They suspect that the cause is the way fructose is metabolised.
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It's also quite easily metabolised and is not as toxic as some other similar drugs.
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According to Kanther, the enzyme, which metabolises the antifreeze, also metabolised the alcohol in the vodka, giving time for the antifreeze to pass in a non-toxic form.
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But that ignores the role of hormones and appetite; differences in the way different foods are metabolised and the way the body reacts to prolonged deprivation by hoarding fat and slowing down.
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"These results cannot be generalised to all sweeteners because the main types of different sweeteners commonly incorporated into our foods and drinks (including sucralose, aspartame, saccharin and Ace-K) are metabolised differently and therefore will have different health effects," said Sarah Berry in a statement by the UK's Science Media Centre.
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Succinylcholine is metabolised by butyrylcholinesterase (aka psuedocholinesterase or plasma cholinesterase).
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Globulin is metabolised into amino acids that are then released into circulation.
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CYP2E1 catalyses the formation of benzyl alcohol and p-cresol, while CYP2B6 produces comparatively little p-cresol. It is believed that in humans, benzyl alcohol is metabolised to benzaldehyde by CYP rather than alcohol dehydrogenase; however, this belief does not appear to be universal. Benzaldehyde is in turn metabolised to benzoic acid, primarily by mitochondrial aldehyde dehydrogenase-2 (ALDH-2), while only a small percentage is metabolised by cytosolic ALDH-1.
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As the drug is partly metabolised via the liver enzyme CYP3A4, strong inducers of this enzyme can decrease its blood plasma concentrations. CYP3A4 inhibitors do not significantly increase vandetanib concentrations, presumably because it is also metabolised by flavin containing monooxygenase 1 (FMO1) and 3.
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Prazepam is metabolised into descyclopropylmethylprazepam (also known as desmethyldiazepam) and 3-hydroxyprazepam which is further metabolised into oxazepam. Prazepam is a prodrug for descyclopropylmethylprazepam/desmethyldiazepam (also known as norprazepam or nordazepam) which is responsible for most of the therapeutic activity of prazepam rather than prazepam itself.
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Ivacaftor is extensively metabolised in humans. In vitro and in vivo data indicate that ivacaftor is primarily metabolised by CYP3A. M1 and M6 are the two major metabolites of ivacaftor in humans. M1 has approximately one-sixth the potency of ivacaftor and is considered pharmacologically active.
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Zaleplon is primarily metabolised by aldehyde oxidase, and its half-life can be affected by substances which inhibit or induce aldehyde oxidase. Taken orally, zaleplon reaches full concentration in about one hour. It is extensively metabolised into 5-oxozaleplon and 5-oxodesethylzaleplon (the latter via desethylzaleplon), with less than 1% of it excreted intact in urine.
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Beta emitting phosphorus-32 (32P), as sodium phosphate, is used to treat overactive bone marrow, in which it is otherwise naturally metabolised.
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Clorazepate is completely metabolised to desmethyl-diazepam in the gastrointestinal tract and thus the pharmacological properties of clorazepate are largely due to desmethyldiazepam.
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Etomidate is highly protein-bound in blood plasma and is metabolised by hepatic and plasma esterases to inactive products. It exhibits a biexponential decline.
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Delamanid is metabolised by the liver enzyme CYP3A4; therefore strong inducers of this enzyme can reduce its effectiveness.Pharmazeutische Zeitung: Delamanid: Neuer Wirkstoff gegen multiresistente TB , 9 May 2014.
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Erythromycin is an inhibitor of the cytochrome P450 system, which means it can have a rapid effect on levels of other drugs metabolised by this system, e.g., warfarin.
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Docetaxel is mainly metabolised in the liver by the cytochrome P450 CYP3A4 and CYP3A5 subfamilies of isoenzymes.Anonymous. Taxotere.com for Healthcare Professionals: Pharmacokinetics. Sanofi-aventis U.S. LLC. (23 Sep 2006).
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Nicocodeine (Lyopect, Tusscodin) is an opioid analgesic and cough suppressant, an ester of codeine closely related to dihydrocodeine and the codeine analogue of nicomorphine. It is not commonly used in most countries, but has activity similar to other opiates. Nicocodeine and nicomorphine were introduced in 1957 by Lannacher Heilmittel of Austria. Nicocodeine is metabolised in the liver by demethylation to produce nicomorphine, also known as 6-nicotinoylmorphine, and subsequently further metabolised to morphine.
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Nicodicodine is an opioid developed as a cough suppressant and analgesic. Synthesized in 1904, it is not commonly used, but has activity similar to other opioids. Nicodicodine is metabolised in the liver by demethylation to produce 6-nicotinoyldihydromorphine, and subsequently further metabolised to dihydromorphine. Since the final active metabolite is the slightly stronger opiate dihydromorphine rather than morphine, nicodicodine can be expected to be marginally more potent and longer acting than nicocodeine.
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Nelfinavir's interaction profile is similar to that of other protease inhibitors. Most interactions occur at the level of the Cytochrome P450 isozymes 3A4 and CYP2C19, by which nelfinavir is metabolised.
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Anaesthesia starts with a latency of 30 to 50 seconds and lasts for about 10 to 30 minutes, depending on perfusion. The drug is metabolised by esterases in blood plasma and liver.
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Ambient Water Quality Criteria for Dissolved Oxygen . Env.gov.bc.ca. Retrieved on 2012-05-23. Associated with these photosynthetic rhythms there is a matching pH rhythm as bicarbonate ion is metabolised by plant cells.
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There is no evidence for DMF interaction with cytochrome P450 and the most common efflux and uptake transporters, and therefore no interactions are expected with medicinal products metabolised or transported by these systems.
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Mexiletine is predominantly metabolised by the liver. The pharmacokinetics of mexiletine are preserved with even moderate to severe renal impairment, but dose adjustment may be required when creatinine clearance falls below 10 mL/minute.
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Sulazepam is a benzodiazepine derivative. It is the thioamide derivative of diazepam. It is metabolised into diazepam, desmethyldiazepam and oxydiazepam. It has sedative, muscle relaxant, hypnotic, anticonvulsant and anxiolytic properties like those of other benzodiazepines.
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Only a small portion of roxithromycin is metabolised. Most of roxithromycin is secreted unchanged into the bile and some in expired air. Under 10% is excreted into the urine. Roxithromycin's half-life is 12 hours.
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Colonies of S. bovinus do not overlap, which indicates they suppress each other's growth. The median lifespan of a colony was estimated to be 36 years. Field work conducted in Swedish pine forests suggested that S. variegatus suppressed the growth of S. bovinus, as there was a negative correlation in occurrence. Suillus bovinus fruit bodies attacked by the yellow mould Dicranophora fulva A Finnish study published in 1997 found that bacterial communities under P. sylvestris without mycorrhizae metabolised organic and amino acids, while communities among S. bovinus metabolised mannitol, a sugar alcohol.
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No pharmacokinetic interactions with doxorubicin were observed in studies. Being a monoclonal antibody, olaratumab is neither metabolised by cytochrome P450 liver enzymes nor transported by transmembrane pumps, and is thus not expected to interact relevantly with other drugs.
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THCB has rarely been isolated from cannabis samples, but appears to be less commonly present than THC or THCV. It is metabolised in a similar manner to THC. Similarly to THC, it has 7 double bond isomers and 30 stereoisomers.
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Pettersson showed that, on a molar basis, glucose and fatty acids were metabolised by hypothermically perfused kidneys at about the same rates. The cortex of the hypothermic dog kidney was shown by Huang to lose lipid (35% loss of total lipid after 24 hours) unless oleate was added to the kidney perfusate. Huang commented that this loss could affect the structure of the cell and that the loss also suggested that the kidney was utilising fatty acid. In a later publication Huang showed that dog kidney cortex slices metabolised fatty acids, but not glucose, at 10 °C.
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The structures of the most abundant (−)-epicatechin metabolites present in the systemic circulation and in urine are depicted. Catechins are metabolised upon uptake from the gastrointestinal tract, in particular the jejunum, and in the liver, resulting in so-called structurally-related epicatechin metabolites (SREM). The main metabolic pathways for SREMs are glucuronidation, sulfation and methylation of the catechol group by catechol- O-methyl transferase, with only small amounts detected in plasma. The majority of dietary catechins are however metabolised by the colonic microbiome to gamma-valerolactones and hippuric acids which undergo further biotransformation, glucuronidation, sulfation and methylation in the liver.
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Combination with non-selective MAO inhibitors might be dangerous. Due to its affinity to the liver enzyme CYP2C9, interactions with drugs being metabolised by this enzyme are also possible, but unlikely. No interaction with tolbutamide, a 2C9 substrate, was observed in studies.
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These metabolites further increase the duration of drug action compared to benzodiazepines that produce nonactive metabolites. Flunitrazepam is lipophilic and is metabolised by the liver via oxidative pathways. The enzyme CYP3A4 is the main enzyme in its phase 1 metabolism in human liver microsomes.
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These enzymes belong to cytochrome P450 group present in the smooth endoplasmic reticulum. Artemisinin derivatives are metabolised differently. They are first converted to dihydroartemisinin (DHA). DHA itself is a strong antimalarial molecule and is active in the blood circulation for two to three hours.
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Furthermore, methods were developed which indirectly detect the glucose concentration via the concentration of metabolised products, e.g. by the consumption of oxygen using fluorescence- optical sensors. Finally, there are enzyme-based concepts that use the intrinsic absorbance or fluorescence of (fluorescence-labeled) enzymes as reporters.
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However, it has complex pharmacokinetics as most of the administered dose is metabolised by hydrolysis of the ester link to the water-insoluble compound O-2372, thus producing a biphasic effects profile that is less suitable for research purposes than the related compound O-2545.
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Licarbazepine is metabolised by conjugation with Glucuronic acid. Approximately 4% are oxidised to the inactive 10,11-dihydroxy derivative. Elimination is almost completely renal, with faeces accounting to less than 4%. 80% of the excreted substances are to be attributed to licarbazepine or its glucuronides.
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Unlike the majority of ACE inhibitors, captopril is not administered as a prodrug (the only other being lisinopril). About 70% of orally administered captopril is absorbed. Bioavailability is reduced by presence of food in stomach. It is partly metabolised and partly excreted unchanged in urine.
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Prednisone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive properties. Prednisone is a prodrug; it is metabolised in the liver by 11-β-HSD to prednisolone, the active drug. Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone.
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Tegafur is a chemotherapeutic prodrug of 5-fluorouracil (5-FU) used in the treatment of cancers. It is a component of the combination drug tegafur/uracil. When metabolised, it becomes 5-FU. It was patented in 1967 and approved for medical use in 1972.
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Salmon calcitonin is rapidly absorbed and eliminated. Peak plasma concentrations are attained within the first hour of administration. Animal studies have shown that calcitonin is primarily metabolised via proteolysis in the kidney following parenteral administration. The metabolites lack the specific biological activity of calcitonin.
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Most of the drug is metabolised; very little diazepam is excreted unchanged. The elimination half-life of diazepam and also the active metabolite desmethyldiazepam increases significantly in the elderly, which may result in prolonged action, as well as accumulation of the drug during repeated administration.
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Avizafone (Pro-Diazepam) is a water-soluble prodrug of the benzodiazepine derivative diazepam. It can be administered intramuscularly. Avizafone is metabolised by enzymes in the blood to form the active drug diazepam. It is used mainly as an antidote to poisoning with organophosphate nerve agents.
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Diagram of new and regenerated production Bio-available nitrogen occurs in the ocean in several forms, including simple ionic forms such as nitrate (NO3−), nitrite (NO2−) and ammonium (NH4+), and more complex organic forms such as urea ((NH2)2CO). These forms are used by autotrophic phytoplankton to synthesise organic molecules such as amino acids (the building blocks of proteins). Grazing of phytoplankton by zooplankton and larger organisms transfers this organic nitrogen up the food chain and throughout the marine food-web. When nitrogenous organic molecules are ultimately metabolised by organisms, they are returned to the water column as ammonium (or more complex molecules that are then metabolised to ammonium).
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Figure: new and regenerated production Bio-available nitrogen occurs in the ocean in several forms, including simple ionic forms such as nitrate (NO3−), nitrite (NO2−) and ammonium (NH4+), and more complex organic forms such as urea ((NH2)2CO). These forms are utilised by autotrophic phytoplankton to synthesise organic molecules such as amino acids (the building blocks of proteins). Grazing of phytoplankton by zooplankton and larger organisms transfers this organic nitrogen up the food chain and throughout the marine food-web. When nitrogenous organic molecules are ultimately metabolised by organisms, they are returned to the water column as ammonium (or more complex molecules that are then metabolised to ammonium).
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First, unlike glucose, which is metabolised throughout the body, the fructose produced from the breakdown of sucrose is metabolised almost exclusively in the liver, where much of it is converted to fat. Secondly, since it is not uncommon for people to take as much as 30 % of their daily caloric intake as sucrose, this consumption crowds out more desirable foods and can sometimes lead to deficiencies of certain nutrients. Thirdly, since many people find sucrose appetising, it is often taken in excess of caloric requirements, thus leading to obesity. The author then turns to the evidence that the consumption of sucrose is associated with certain specific disorders other than obesity.
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Based on the analysis of rat and human urine by gas chromatography and mass spectrometry, mephedrone is thought to be metabolised by three phase 1 pathways. It can be demethylated to the primary amine (producing compounds 2, 3 and 5), the ketone group can be reduced (producing 3) or the tolyl group can be oxidised (producing 6). Both 5 and 6 are thought to be further metabolised by conjugation to the glucuronide and sulfate derivatives. Knowledge of the primary routes of metabolism should allow the intake of mephedrone to be confirmed by drug tests, as well as more accurate determination of the causes of side effects and potential for toxicity.
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It is contraindicated in patients with cystitis and urinary tract infections. It is sparingly metabolised in the liver to two inactive metabolites. Most of the drug is eliminated unchanged in the urine. Renal disease impairs excretion, and it should be used with caution in renal disease.
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Dihydrocodeine is metabolised by the CYP450 system isoenzyme 2D6 to dihydromorphine, which mediates the majority of its analgesic effects. Owing to the low oral bioavailibility of dihydrocodeine (20%), and its subsequent metabolism to active compounds, it is likely that doses below 30mg are sub therapeutic for analgesia.
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They come in a number of strengths including 5%, 10%, and 50% dextrose. While they may start out hypertonic they become hypotonic solutions as the sugar is metabolised. Versions are also available mixed with saline. Dextrose solutions for medical use became available in the 1920s and 1930s.
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Elimination took place for 90% through urine and 10% through faeces. After 72 hours 1.5% of the dose was still present in tissue. The highest concentration levels were present in liver, kidney and fat. BTC is rapidly metabolised via hydrolysis to benzoic acid and hydrochloric acid.
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It is unique amongst uncouplers in displaying broad-spectrum activity against fungi and also very low toxicity to mammals due to it being rapidly metabolised to a compound without uncoupling activity. It was first described in 1992 and was developed by researchers at the Japanese company Ishihara Sangyo Kaisha.
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Following oral administration, camazepam is almost completely absorbed into the bloodstream, with 90 percent bioavailability achieved in humans. In the human camazepam is metabolised into the active metabolite temazepam. Studies in dogs have shown that the half-life of the terminal elimination phase ranged from 6.4 to 10.5 h.
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Haemoglobin may be excreted through urine, causing haemoglobinuria. The sudden release of haemoglobin will also pass through the liver and be metabolised into bilirubin, which in high concentrations, accumulates under the skin to cause jaundice. Liberation of blood cell debris into the circulation will also cause disseminated intravascular coagulation.
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After oral administration of 100 mg tilidine plus 8 mg naloxone, the maximum effect is reached in about 25-50 minutes. The duration of action is given as 4-6 hours. The elimination half-life for nortilidine is 3-5 hours. Tilidine is metabolised to 90% and eliminated renally.
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After oral administration, peak serum concentration is reached after 1–2 hours and up to 99% of the drug is bound to plasma proteins. The majority of ibuprofen is metabolised and eliminated within 24 hours in the urine; however, 1% of the unchanged drug is removed through biliary excretion.
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In humans moclobemide is rapidly and almost completely absorbed and totally metabolised via the liver. Peak plasma levels occur 0.3 to 2 hours after oral administration. The bioavailability increases during the first week of therapy from 60% to 80% and more. The elimination half-life is around 2 hours.
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After oral ingestion, glycyrrhizin is first hydrolysed to 18β-glycyrrhetinic acid (enoxolone) by intestinal bacteria. After complete absorption from the gut, 18β-glycyrrhetinic acid is metabolised to 3β-monoglucuronyl-18β-glycyrrhetinic acid in the liver. This metabolite then circulates in the bloodstream. Consequently, its oral bioavailability is poor.
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Opicapone is a weak inhibitor of the liver enzymes CYP1A2, CYP2B6, CYP2C8, and CYP2C9. The only CYP interaction found in studies that is somewhat likely to be relevant is that with repaglinide, which is metabolised by CYP2C8. The metabolism of warfarin, a CYP2C9 substrate, is not measurably affected.
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Rhododendrol is metabolised via tyrosinase-catalysed oxidation. Therefore, the enzyme tyrosinase is necessary for the oxidation of rhododendrol. Tyrosinase regularly plays an essential role in the production of melanocytes called the melanogenesis. After oxidation of rhododendrol by the tyrosinase enzyme, several kinds of phenols and catechols are formed.
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The pharmacological effects of triazolam are similar to those of most other benzodiazepines. It does not generate active metabolites. Triazolam is a short-acting benzodiazepine, is lipophilic, and is metabolised hepatically via oxidative pathways. The main pharmacological effects of triazolam are the enhancement of the neurotransmitter GABA at the GABAA receptor.
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Iproniazid can also be metabolised by O-dealkylation from iproniazid to acetone and isoniazid. Isoniazid can undergo further metabolism via multiple metabolic pathways, of which one eventually results in alkylating agents as well. This toxifying metabolic pathway includes N-acetylation. Reactions involving acetylation are influenced by genetic variance: the acetylator phenotype.
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Bendamustine is a white, water- soluble microcrystalline powder with amphoteric properties. It acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases. After intravenous infusion it is extensively metabolised in the liver by cytochrome p450. More than 95% of the drug is bound to protein – primarily albumin.
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He became a fan favourite at the club due to his combative style of play. In 2007, he transferred to Israeli club Maccabi Haifa. While playing for Volta Redonda in the Campeonato Carioca in 2010, Paulinho tested positive for Benzoylecgonine, a metabolised version of cocaine. He was subsequently banned for two years.
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Most statins are metabolised in part by one or more hepatic cytochrome P450 enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). The primary metabolism pathway of pitavastatin is glucuronidation. It is minimally metabolized by the CYP450 enzymes CYP2C9 and CYP2C8,Drugs.com: Livalo .
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Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed. The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein.
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Velpatasvir reaches highest blood plasma levels three hours after oral intake together with sofosbuvir. Plasma protein binding is over 99.5%. It is slowly metabolised by the liver enzymes CYP2B6, CYP2C8 and CYP3A4. While monohydroxylated and demethylated metabolites have been identified in human blood plasma and faeces, over 98% of the circulating substance is velpatasvir itself.
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Since Pirfenidone is metabolised through the CYP1A2 enzyme pathway, any drug which inhibits this enzyme is likely to precipitate the toxicity of pirfenidone: concomitant therapy is to be avoided. Fluvoxamine is contraindicated in patients who are on treatment with pirfenidone. Other inhibitors of CYP1A2 such as ciprofloxacin, amiodarone and propafenone should be used with caution.
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Icodextrin is not significantly metabolised inside the peritoneum. Instead, it is absorbed slowly (40% after 12 hours) into the bloodstream via the lymph vessels. There it is broken down into oligosaccharides by the enzyme alpha-amylase. In patients with intact kidney function, both icodextrin and its fragments are excreted via the kidney by glomerular filtration.
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Triclofos is a sedative drug used rarely for treating insomnia. Triclofos is a prodrug which is metabolised in the liver into the active drug trichloroethanol. The half-life of triclofos is fairly long and it may cause drowsiness the next day. Trichloroethanol may cause liver damage and triclofos should not be used for extended periods.
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On average, it takes about one hour for the body to metabolise (break down) one unit of alcohol. However, this will vary with body weight, sex, age, personal metabolic rate, recent food intake, the type and strength of the alcohol, and medications taken. Alcohol may be metabolised more slowly if liver function is impaired.
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Urinary VMA is elevated in patients with tumors that secrete catecholamines. These urinalysis tests are used to diagnose an adrenal gland tumor called pheochromocytoma, a tumor of catecholamine-secreting chromaffin cells. These tests may also be used to diagnose neuroblastomas, and to monitor treatment of these conditions. Norepinephrine is metabolised into normetanephrine and VMA.
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Apremilast is absorbed from the gut well (73%) and independently of food intake, and reaches peak blood plasma concentrations after 2.5 hours. Plasma protein binding is 68%. It is metabolised in the liver, mainly via the enzyme CYP3A4, but to a minor extent via CYP1A2 and CYP2A6. The main metabolite is O-desmethylapremilast glucuronide.
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It has to be taken for about three months to achieve a steady-state concentration. In the blood, it is almost completely (90–96%) bound to plasma proteins such as albumin. It is metabolised to N-desmethylvandetanib via CYP3A4 and to vandetanib-N-oxide via FMO1 and 3. Both of these are active metabolites.
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Dimethyl fumarate is a lipophilic, highly mobile molecule in human tissue. As an α,β-unsaturated electrophilic compound, DMF is rapidly attacked by the detoxifying agent glutathione (GSH) in a Michael addition reaction. Through these reactions, it is metabolised to monomethyl fumarate (MMF) prior to entering systemic distribution. DMF has been described a prodrug.
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Approximately 75% of a dose of galantamine is metabolised in the liver. In vitro studies have shown that Hepatic CYP2D6 and CYP3A4 are involved in galantamine metabolism. Within 24 hours of intravenous or oral administration approximately 20% of a dose of galantamine will be excreted unreacted in the urine. In humans, several metabolic pathways for galantamine exist.
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Parathyroid hormone is a natural peptide that is not metabolised in the liver. It is not protein bound and has a low volume of distribution, therefore no specific drug-drug interactions are suspected. From the knowledge of the mechanism of action, combined use of Preotact and cardiac glycosides may predispose patients to digitalis toxicity if hypercalcemia develops.
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Thiamine deficiency and errors of thiamine metabolism are believed to be the primary cause of Wernicke encephalopathy. Thiamine, also called B1, helps to break down glucose. Specifically, it acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine is first metabolised to its more active form, thiamine diphosphate (TDP), before it is used.
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Convallatoxin is mainly metabolised in the liver by the conversion of convallatoxin into convallatoxol. For this, the aldehyde (-CHO) group attached to C¬10 is reduced to an alcohol group (-CH2OH) by cytochrome P450 reductase (CYP450). This is a phase I metabolism reaction. However, further modification through a phase II reaction of convallatoxin has not been found.
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Sunitinib's peak plasma level is reached 6–12 hours post-dose. The drug is 95% protein bound and has a volume of distribution of 2230 L, which indicates distribution into tissues. Sunitinib is metabolised mostly by CYP3A4 and has a half life of 40–60 hours. Nintedanib reaches maximum plasma concentration 2–4 hours post-dose.
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Nitrazepam is a nitrobenzodiazepine. It is a 1,4 benzodiazepine, with the chemical name 1,3-Dihydro-7-nitro-5-phenyl-2H-1,4- benzodiazepin-2-one. It is long acting, lipophilic, and metabolised hepatically by oxidative pathways. It acts on benzodiazepine receptors in the brain which are associated with the GABA receptors, causing an enhanced binding of GABA to GABAA receptors.
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They control spermatogenesis and the ovarian cycle, parturition, lactation, and maternal behaviour. They control the body's response to stress and infection. They regulate the body's metabolism, influencing eating and drinking behaviour, and influence how energy intake is utilised, that is, how fat is metabolised. They influence and regulate mood, body fluid and electrolyte homeostasis, and blood pressure.
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Xylose is metabolised by humans, although it is not a major human nutrient and is largely excreted by the kidneys. Humans can obtain xylose only from their diet. An oxidoreductase pathway is present in eukaryotic microorganisms. Humans have enzymes called protein xylosyltransferases (XYLT1, XYLT2) which transfer xylose from UDP to a serine in the core protein of proteoglycans.
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Different hormones are produced in different zones of the cortex and medulla of the gland. Light microscopy at magnification × 204. The adrenal gland secretes a number of different hormones which are metabolised by enzymes either within the gland or in other parts of the body. These hormones are involved in a number of essential biological functions.
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Amitriptyline inhibits neuronal reuptake of serotonin and noradrenaline from the synapse in the central nervous system; this increases their availability in the synapse to cause neurotransmission on the post-synaptic neurone. Amitriptyline is metabolised by cytochrome P450 enzymes in the liver to nortriptyline, which also acts as a noradrenaline reuptake inhibitor; this potentiates the antidepressant effects of amitriptyline.
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Myrophine (Myristylbenzylmorphine) is an opiate analogue that was developed in 1952. It is a derivative of morphine. Myrophine is substituted with a 3-benzyl group and a 6-myristyl chain. It is metabolised to form benzylmorphine and then further to morphine, and so is a long-acting prodrug for morphine, but with a slow onset of effects.
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Only 5–10% of L-DOPA crosses the blood–brain barrier. The remainder is often metabolised to dopamine elsewhere, causing a wide variety of side effects including nausea, dyskinesias, and stiffness. Carbidopa and benserazide are peripheral dopa decarboxylase inhibitors. They inhibit the metabolism of L-DOPA in the periphery, thereby increasing levodopa delivery to the central nervous system.
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Relatively small amounts of diluent are used in a rebreather, as the inert components are neither metabolised nor exhausted to the environment while the diver remains at depth, but are rebreathed repetitively, only being lost during ascent, when the gas expands in inverse proportion to the pressure, and must be vented to maintain the correct volume in the loop.
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These phenols and catechols together form ortho- quinones (o-quinones) . Presence of o-quinones can lead to cytotoxicity via the production of reactive oxygen species (ROS) or by the binding to enzymes or DNA . When rhododendrol is metabolised via the tyrosinase-catalysed oxidation RD-quinone will be formed . This formation gives rise to the formation of secondary quinones.
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Candesartan is marketed as the cyclohexyl 1-hydroxyethyl carbonate (cilexetil) ester, known as candesartan cilexetil. Candesartan cilexetil is metabolised completely by esterases in the intestinal wall during absorption to the active candesartan moieity. The use of a prodrug form increases the bioavailability of candesartan. Despite this, absolute bioavailability is relatively poor at 15% (candesartan cilexetil tablets) to 40% (candesartan cilexetil solution).
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Maintenance of that order requires continual exchange of information between the organism and its surroundings. In higher organisms, information is acquired mainly through sensory receptors and metabolised in the nervous system. The result is action – some form of motion, for example locomotion, speech, internal motion of organs, secretion of hormones, etc. The reactions of one organism become an informational signal to other organisms.
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Clopidogrel is an inactive prodrug that partially depends on CYP2C19 for conversion to its active form. Inhibition of CYP2C19 may block the activation of clopidogrel, which could reduce its effects. Almost all benzodiazepines are metabolised by the CYP3A4 and CYP2D6 pathways, and inhibition of these enzymes results in a higher AUC (i.e., the total effect over time of a given dose).
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Parathyroid hormone is metabolised in the liver and to a lesser extent in the kidney. It is not excreted from the body in its intact form. Circulating carboxy-terminal fragments are filtered by the kidney, but are subsequently broken down into even smaller fragments during tubular reuptake. No studies have so far been performed in patients with severe hepatic impairment.
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There is no treatment for cortisone reductase deficiency. Shots of cortisol are quickly metabolised into cortisone by the dysregulated 11β-HSD1 enzyme; however, symptoms can be treated. Treatment of hyperandroginism can be done through prescription of antiandrogens. They do so by inhibiting the release of gonadotropin and luteinizing hormone, both hormones in the pituitary, responsible for the production of testosterone.
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Cortisol increases glomerular filtration rate, and renal plasma flow from the kidneys thus increasing phosphate excretion, as well as increasing sodium and water retention and potassium excretion by acting on mineralocorticoid receptors (cortisol can be metabolised into cortisone which acts on the receptor, mimicking the effect of aldosterone). It also increases sodium and water absorption and potassium excretion in the intestines.
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Codeine is an opioid and an agonist of the mu opioid receptor. It acts on the central nervous system to have an analgesic effect. It is metabolised in the liver to produce morphine which is ten times more potent against the mu receptor. Opioid receptors are G-Protein coupled receptors that positively and negatively regulate synaptic transmission through downstream signalling.
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Sodium picosulfate is a prodrug. It has no significant direct physiological effect on the intestine; however, it is metabolised by gut bacteria into the active compound 4,4'-dihydroxydiphenyl-(2-pyridiyl)methane (DPM, BPHM). This compound is a stimulant laxative and increases peristalsis in the gut. Sodium picosulfate is typically prescribed in a combined formulation with magnesium citrate, an osmotic laxative.
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Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam. Clorazepate is a long-acting benzodiazepine drug. Clorazepate produces the active metabolite desmethyl-diazepam, which is a partial agonist of the GABAA receptor and has a half life of 20 – 179 hours; a small amount of desmethyldiazepam is further metabolised into oxazepam.
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Midazolam is a short-acting benzodiazepine in adults with an elimination half-life of 1.5–2.5 hours. In the elderly, as well as young children and adolescents, the elimination half-life is longer. Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam. Age-related deficits, renal and liver status affect the pharmacokinetic factors of midazolam as well as its active metabolite.
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One dietary Calorie contains 4184 joules of energy. The human body is a highly complex biochemical system that undergoes processes which regulate energy balance. The metabolic pathways for protein are less efficient than the metabolic pathways for carbohydrates and fat. Protein contains four calories per gram, although a large part of the calories are lost as heat when metabolised by the body.
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Glucose metabolism and various forms of it in the process Glucose-containing compounds and isomeric forms are digested and taken up by the body in the intestines, including starch, glycogen, disaccharides and monosaccharides. Glucose is stored in mainly the liver and muscles as glycogen. It is distributed and used in tissues as free glucose. In humans, glucose is metabolised by glycolysis and the pentose phosphate pathway.
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Its oral bioavailability is over 80% and is extensively metabolised to its active form upon first-pass through the liver. It has a volume of distribution of 23–26 litres. Its half-life is about 1–3 hours and its active carboxylate metabolite has a half-life of 6–10 hours. More than 90% of the oral dose is eliminated in the urine as the active metabolite.
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Clonazepam is lipid- soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine. Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines.
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Diagnosis of Fatty-acid metabolism disorder requires extensive lab testing. Normally, in cases of hypoglycaemia, triglycerides and fatty acids are metabolised to provide glucose/energy. However, in this process, ketones are also produced and ketotic hypoglycaemia is expected. However, in cases where fatty acid metabolism is impaired, a non-ketotic hypoglycaemia may be the result, due to a break in the metabolic pathways for fatty-acid metabolism.
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Sumatriptan is metabolised primarily by monoamine oxidase A into 2‐{5‐[(methylsulfamoyl)methyl]‐indole‐3‐yl}acetic acid which is then conjugated to glucuronic acid. These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged. There is no simple, direct relationship between sumatriptan concentration (pharmacokinetics) per se in the blood and its anti-migraine effect (pharmacodynamics).
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All three dietary monosaccharides are transported into the liver by the GLUT2 transporter. Fructose and galactose are phosphorylated in the liver by fructokinase (Km= 0.5 mM) and galactokinase (Km = 0.8 mM), respectively. By contrast, glucose tends to pass through the liver (Km of hepatic glucokinase = 10 mM) and can be metabolised anywhere in the body. Uptake of fructose by the liver is not regulated by insulin.
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Morphine is metabolised primarily in the liver and approximately 87% of a dose of morphine is excreted in the urine within 72 h of administration. Morphine is metabolized primarily into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) via glucuronidation by phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 (UGT2B7). About 60% of morphine is converted to M3G, and 6% to 10% is converted to M6G.
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Acetaldehyde is metabolised to acetate by acetaldehyde dehydrogenase (ALDH), which is found predominantly in liver mitochondria. Acetate is used by the muscle cells to produce acetyl-CoA using the enzyme acetyl-CoA synthetase, and the acetyl-CoA is then used in the citric acid cycle.Smith, C., Marks, Allan D., Lieberman, Michael, 2005, Marks' Basic Medical Biochemistry: A Clinical Approach, 2nd ed., Lippincott Williams & Wilkins, USA, p.
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Brompheniramine works by acting as an antagonist of histamine H1 receptors. It also functions as a moderately effective anticholinergic agent, and is likely an antimuscarinic agent similar to other common antihistamines such as diphenhydramine. Brompheniramine is metabolised by cytochrome P450s. The halogenated alkylamine antihistamines all exhibit optic isomerism and brompheniramine products contain racaemic brompheniramine maleate whereas dexbrompheniramine (Drixoral) is the dextrorotary (right-handed) stereoisomer.
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DES is not metabolised as quickly as endogenous estrogen. DES remains bound to cytosolic receptors for a longer period of time. The extended binding time of DES and the subsequent prolonged activation of its cognate receptors has been suggested to disrupt Mullerian development, resulting in uterine abnormalities. Exposure to DES induced multiple uterine abnormalities including constriction bands, hypoplasticity in the uterine cavity and irregular borders.
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Panobinostat is absorbed quickly and almost completely from the gut, but has a significant first-pass effect, resulting in a total bioavailability of 21%. Highest blood plasma levels in patients with advanced cancer are reached after two hours. Plasma protein binding is about 90%. The substance is metabolised mainly through oxidation by the liver enzyme CYP3A4 and to a small extent by CYP2D6 and CYP2C19.
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Pyrazinamide is well absorbed orally. It crosses inflamed meninges and is an essential part of the treatment of tuberculous meningitis. It is metabolised by the liver and the metabolic products are excreted by the kidneys. Pyrazinamide is routinely used in pregnancy in the UK and the rest of the world; the World Health Organization (WHO) recommends its use in pregnancy; and extensive clinical experience shows that it is safe.
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Ghanayem et al., 1985 Committee on Acute Exposure Guideline Levels; Committee on Toxicology; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Research Council. Washington (DC): National Academies Press (US); 2014 Mar 21 Secondly, methacrylonitrile can be metabolised in the liver by CYP2E1 (a Cytochrome-P450 enzyme). This is the most important enzyme for the oxidative metabolism, but also other cytochrome P-450 enzymes may be involved.
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Arachidonic acid is metabolised, via cyclooxygenase (COX) and lipoxygenase, to various substances including prostaglandins and leukotrienes, which exhibit potent pro-inflammatory and vasoactive effects. By inhibiting COX, and more specifically COX-2, (either through selective or non-selective drugs) inflammation and oedema can be reduced. However, COX inhibitors may induce peptic ulcers and cause hyperkalemia and hypernatremia. Additionally, COX inhibitors have not shown any great response in the treatment of MAS.
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Alcohol is metabolized by a normal liver at the rate of about 8 grams of pure ethanol per hour. 8 grams or is one British standard unit. An "abnormal" liver with conditions such as hepatitis, cirrhosis, gall bladder disease, and cancer is likely to result in a slower rate of metabolism. Ethanol is metabolised to acetaldehyde by alcohol dehydrogenase (ADH), which is found in many tissues, including the gastric mucosa.
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The Schmutzdecke consists of bacteria, fungi, protozoa, rotifera and a range of aquatic insect larvae. As the biofilm ages, more algae may develop and larger aquatic organisms including bryozoa, snails and Annelid worms may be present. As water passes through the hypogeal layer, particles of matter are trapped in the mucilaginous matrix and soluble organic material is adsorbed. The contaminants are metabolised by the bacteria, fungi and protozoa.
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Trifluridine is metabolised by the enzyme thymidine phosphorylase to 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (FTY), and also by glucuronidation. Elimination half-life is 1.4 hours on the first day and increases to 2.1 hours on the twelfth day. It is mainly excreted via the kidneys. Tipiracil causes Cmax (highest blood plasma concentrations) of trifluridine to increase 22-fold, and its area under the curve 37-fold, by inhibiting thymidine phosphorylase.
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Therefore, in cases of overdose, repeat doses of flumazenil may be required to prevent recurrent symptoms once the initial dose of flumazenil wears off. It is hepatically metabolised to inactive compounds which are excreted in the urine. Individuals who are physically dependent on benzodiazepines may suffer benzodiazepine withdrawal symptoms, including seizure, upon rapid administration of flumazenil. It is not recommended for routine use in those with a decreased level of consciousness.
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There are 33 Slow Sand Filter beds at Coppermills water treatment works, which occupy much of the south and east of the site. The sand bed in the filters support a gelatinous biofilm or hypogeal layer in the top few millimetres of the sand. The surface biofilm provides an effective biological treatment. Water passes through the hypogeal layer where contaminants are retained and metabolised by the bacteria, fungi and protozoa.
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CDCA and other bile acids form micelles, which facilitate lipid digestion. After absorption, they are taken up by the liver and resecreted, so undergoing an enterohepatic circulation. Unabsorbed CDCA can be metabolised by bacteria in the colon to form the secondary bile acid, lithocholic acid or the epimer, ursodeoxycholic acid. CDCA is the most potent natural bile acid at stimulating the nuclear bile acid receptor, farnesoid X receptor (FXR).
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Peak plasma concentrations are achieved one to three hours after a dose, and the plasma half-life is 1.0 to 2.5 hours. It is extensively metabolised to inactive metabolites, principally the 6-carboxy derivative, which are excreted in the urine. About 70% of a dose of oxamniquine is excreted as the 6-carboxy metabolite within 12 hours of a dose; traces of the 2-carboxy metabolite have also been detected in the urine.
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The fluoropyrimidines include fluorouracil and capecitabine. Fluorouracil is a nucleobase analogue that is metabolised in cells to form at least two active products; 5-fluourouridine monophosphate (FUMP) and 5-fluoro-2'-deoxyuridine 5'-phosphate (fdUMP). FUMP becomes incorporated into RNA and fdUMP inhibits the enzyme thymidylate synthase; both of which lead to cell death. Capecitabine is a prodrug of 5-fluorouracil that is broken down in cells to produce the active drug.
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The five most abundant of these metabolites were found in the abdomen of the bee. Within the first hour of ingestion, acetamiprid concentrations were highest in tissues with a high nicotinic acetylcholine receptor density such as the abdomen, thorax and head. Acetamiprid was rapidly distributed throughout the bee’s body, but also rapidly metabolised into the seven compounds. The substance is not just broken down in the gut, but in the entire body of the bee.
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Acetyldihydrocodeine is an opiate derivative discovered in Germany in 1914 and was used as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates. Acetyldihydrocodeine is a very close relative derivative of Thebacon, where only the 6-7 bond is unsaturated. Acetyldihydrocodeine can be described as the 6-acetyl derivative of dihydrocodeine and is metabolised in the liver by demethylation and deacetylation to produce dihydromorphine.
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In human trials on healthy volunteers, TPA-023 was comparable to lorazepam, but had much less side effects on cognition, memory, alertness or coordination. In Phase II trials, the compound was significantly superior to placebo without inducing sedation. The clinical development was halted due to preclinical toxicity (cataract) in long term dosing studies. TPA-023 is well absorbed following oral administration and extensively metabolised by the liver, with a half-life of 6.7 hours.
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Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems. In healthy individuals, it is metabolised (hydroxylated) into tyrosine, another amino acid, by phenylalanine hydroxylase. However, this enzyme requires tetrahydrobiopterin as a cofactor and thus its deficiency slows phenylalanine metabolism.
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Butylone was first synthesized by Koeppe, Ludwig and Zeile which is mentioned in their 1967 paper. It remained an obscure product of academia until 2005 when it was sold as a designer drug. Butylone shares the same relationship to MBDB as methylone does to MDMA ("Ecstasy"). Formal research on this chemical was first conducted in 2009, when it was shown to be metabolised in a similar manner to related drugs like methylone.
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Ball and stick model of ammonia; one nitrogen atom with three hydrogen atoms. Accumulation of ammonia in the bloodstream is associated with hepatic encephalopathy. There are various explanations why liver dysfunction or portosystemic shunting might lead to encephalopathy. In healthy subjects, nitrogen-containing compounds from the intestine, generated by gut bacteria from food, are transported by the portal vein to the liver, where 80–90% are metabolised through the urea cycle and/or excreted immediately.
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Oxcarbazepine is a prodrug, which is largely metabolised to its pharmacologically active 10-monohydroxy derivative licarbazepine (sometimes abbreviated MHD). Oxcarbazepine and MHD exert their action by blocking voltage-sensitive sodium channels, thus leading to the stabilization of hyper- excited neural membranes, suppression of repetitive neuronal firing and diminishment propagation of synaptic impulses. Furthermore, anticonvulsant effects of these compounds could be attributed to enhanced potassium conductance and modulation of high-voltage activated calcium channels.
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Azaribine (triacetyl-6-azauridine) is a drug which was developed for the treatment of psoriasis, and also has anti-cancer and antiviral actions. It is a prodrug which is metabolised to the nucleoside analogue 6-azauridine in the body. Azaribine was approved for clinical use in treatment of psoriasis, but subsequently withdrawn because of toxicity issues, however it continues to be researched as a potential agent for the treatment of emerging viral diseases.
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Because of low water solubility, kidneys are not able to secrete them in urine as such. They must be metabolised to more water-soluble metabolites, but metabolism, especially in humans, is extremely slow. This results in biological half-lives of several years for all dioxins. That of TCDD is estimated to be 7 to 8 years, and for other PCDD/Fs from 1.4 to 13 years, PCDFs on average slightly shorter than PCDDs.
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The non-nitrogenous bisphosphonates (diphosphonates) are metabolised in the cell to compounds that replace the terminal pyrophosphate moiety of ATP, forming a non-functional molecule that competes with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone. This type of bisphosphonate has overall more negative effects than the nitrogen containing group, and is prescribed far less often.
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Considered a low-to-medium-potency opioid, tilidine has the oral potency of about 0.2, that is, a dose of 100 mg p.o. is equianalgesic to approximately 20 mg morphine sulfate orally. It is administered orally (by mouth), rectally (by a suppository), or by injection (SC, IM or slowly IV). Tilidine itself is only a weak opioid, but is rapidly metabolised in the liver and gut to its active metabolite nortilidine and then to bisnortilidine.
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Iclazepam (Clazepam) is a drug which is a benzodiazepine derivative. It has sedative and anxiolytic effects similar to those produced by other benzodiazepine derivatives, and is around the same potency as chlordiazepoxide. Iclazepam is a derivative of nordazepam substituted with a cyclopropylmethoxyethyl group on the N1 nitrogen. Once in the body, iclazepam is quickly metabolised to nordazepam and its N-(2-hydroxyethyl) derivative, which are thought to be mainly responsible for its effects.
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Animal experiments show that almost all demeton-S-methyl derivatives are excreted through urine. Most of the demeton-S-methyl is converted to demeton-S-methyl sulfoxide, where an oxygen group is added to the sulfur in the side chain. This sulfoxide can then be further metabolised by adding another oxygen group, creating demeton-S-methyl sulfone. Another pathway to metabolise demeton-S-methyl is to demethylate the oxygen group(s) of demeton.
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The major product of metabolisation by these enzymes is N-desmethylated sildenafil, which is metabolised further. This metabolite also has an affinity for the PDE receptors, about 40% of that of sildenafil. Thus, the metabolite is responsible for about 20% of sildenafil's action. Sildenafil is excreted as metabolites predominantly in the feces (about 80% of administered oral dose) and to a lesser extent in the urine (around 13% of the administered oral dose).
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In the body, acecainide is metabolised in several products. Some acecainide can convert to procainamide. The deacetylation clearance of acecainide is 0.39 L/h compare to a total NAPA clearance of 1.38 L/h, indicating that 2.8% of NAPA was converted to procainamide, 0.3% was desethylated, and 10.3% convert to unidentified metabolites, with 86.6% excreted unchanged. Following oral administration, 59 to 87% of a dose of acecainide is excreted unchanged in the urine.
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The substance is metabolised in the liver, mainly by the enzyme CYP2D6. At least 15 different metabolites are described, including (in animals) N-desalkyl and hydroxy derivatives and glucuronides. Less than 1% is excreted in unchanged form, and the main excretion path is via bile and faeces. Elimination half life varies widely between individuals and is about 5 to 15 hours after a single dose, and 18 to 19 days on average when given daily.
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Monoamine oxidase inhibitors (MAO inhibitors) are another class of drugs blocking catecholamine degradation. Therefore, their combination with opicapone can result in increased catecholamine concentrations in the body and corresponding adverse effects. Combining the antiparkinson MAO inhibitors selegiline or rasagiline with opicapone is considered safe. Potentially, there are also interactions with drugs being metabolised by COMT (for example isoprenaline, epinephrine, dopamine, or dobutamine), tricyclic antidepressants and antidepressants of the norepinephrine reuptake inhibitor type.
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It is a metabolite of etretinate, which was used prior to the introduction of acitretin. Etretinate was discontinued because it had a narrow therapeutic index as well as a long elimination half-life (t1/2=120 days), making dosing difficult. In contrast, acitretin's half-life is approximately 2 days. However, because acitretin can be reverse metabolised into etretinate which has an extremely long half-life, women must avoid becoming pregnant for at least three years after discontinuing acitretin.
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Tiny particles of the pigment can flake off and become airborne, and then are absorbed by the lungs. Alternatively, toxic gas can be released from compounds containing arsenic following certain chemical processes, such as heating, or metabolism by an organism. When the wallpaper becomes damp and moldy, the pigment may be metabolised, causing the release of poisonous arsine gas (). Fungi genera such as Scopulariopsis or Paecilomyces release arsine gas, when they are growing on a substance containing arsenic.
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M. verreauxi is the best at climbing and is thought to be the main pollinator. Rhabdomys pumilio, on the other hand, was sometimes found to be quite destructive of the inflorescences in a laboratory setting. In the field on average 20% of the inflorescences are destroyed within a two month period, and this mouse is thought to be likely responsible. The xylose in the nectar can be metabolised by the intestinal microbiotic flora of the small mouse Micaelamys namaquensis.
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Eslicarbazepine acetate is absorbed to at least 90% from the gut, independently of food intake. It is quickly metabolised to eslicarbazepine, so that the original substance cannot be detected in the bloodstream. Peak plasma levels of eslicarbazepine are reached after 2–3 (1–4) hours, and plasma protein binding is somewhat less than 40%. Biological half-life is 10 to 20 hours, and steady-state concentrations are reached after four to five days after start of the treatment.
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Normal dietary fat contains mostly long-chain triglycerides (LCTs). Medium-chain triglycerides (MCTs) are more ketogenic than LCTs because they generate more ketones per unit of energy when metabolised. Their use allows for a diet with a lower proportion of fat and a greater proportion of protein and carbohydrate, leading to more food choices and larger portion sizes. The original MCT diet developed by Peter Huttenlocher in the 1970s derived 60% of its calories from MCT oil.
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Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the stomach, so can be given orally. Levothyroxine is the pharmaceutical name of the manufactured version of T4, which is metabolised more slowly than T3 and hence usually only needs once-daily administration. Natural desiccated thyroid hormones are derived from pig thyroid glands, and are a "natural" hypothyroid treatment containing 20% T3 and traces of T2, T1 and calcitonin.
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Valpromide (marketed as Depamide by Sanofi-Aventis) is a carboxamide derivative of valproic acid used in the treatment of epilepsy and some affective disorders. It is rapidly metabolised (80%) to valproic acid (another anticonvulsant) but has anticonvulsant properties itself. It may produce more stable plasma levels than valproic acid or sodium valproate and may be more effective at preventing febrile seizures. However, it is over one hundred times more potent as an inhibitor of liver microsomal epoxide hydrolase.
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Bilirubin is conjugated with glucuronic acid in the liver by the enzyme glucuronyltransferase, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Although 95% of the secreted bilirubinoid bile is reabsorbed by the small intestine, conjugated bilirubin is not reabsorbed in small intestine. All conjugated bilirubin in the large intestine is metabolised by colonic bacteria to urobilinogen, which is then further oxidized to urobilin and stercobilin.
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Karyoklepty is a strategy for cellular evolution, whereby a predator cell appropriates the nucleus of a cell from another organism to supplement its own biochemical capabilities. In the related process of kleptoplasty, the predator sequesters plastids (especially chloroplasts) from dietary algae. The chloroplasts can still photosynthesize, but do not last long after the prey's cells are metabolised. If the predator can also sequester cell nuclei from the prey to encode proteins for the plastids, it can sustain them.
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When exposure to toluene occurs there is usually simultaneous exposure to several other chemicals. Often toluene exposure occurs in conjunction with benzene and since they are to some degree metabolised by the same enzymes, the relative concentrations will determine their rate of elimination. Of course the longer it takes for toluene to be eliminated the more harm it is likely to do. The smoking and drinking habits of those exposed to toluene will partially determine the elimination of toluene.
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As opposed to barbital, BZDs are not GABA-receptor activators and rely on increasing the neurotransmitter's natural activity. Bromazepam is an intermediate-acting benzodiazepine, is moderately lipophilic compared to other substances of its class and metabolised hepatically via oxidative pathways. It does not possess any antidepressant or antipsychotic qualities. After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day.
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Human polypeptide C5a contains 74 amino acids and has 11kDa. NMR spectroscopy proved that the molecule is composed of four helices and connected by peptide loops with three disulphide bonds between helix IV and II, III. There is a short 1.5 turn helix on N terminus but all agonist activity take place in the C terminus. C5a is rapidly metabolised by a serum enzyme carboxypeptidase B to a 72 amino acid form C5a des-Arg without C terminal arginine.
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Infants may still be breastfed to provide all of the benefits of breastmilk, but the quantity must also be monitored and supplementation for missing nutrients will be required. The sweetener aspartame, present in many diet foods and soft drinks, must also be avoided, as aspartame is metabolised into phenylalanine. Different people can tolerate different amounts of Phe in their diet. Regular blood tests are used to determine the effects of dietary Phe intake on blood Phe level.
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Mycophenolate can be derived from the fungi Penicillium stoloniferum, P. brevicompactum and P. echinulatum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It reversibly inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes. Other cells recover purines via a separate salvage pathway and are thus able to escape the effect.
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The rate at which cells grow during this phase is known as the growth rate (k), and the time it takes the cells to double is known as the generation time (g). During log phase, nutrients are metabolised at maximum speed until one of the nutrients is depleted and starts limiting growth. The third phase of growth is the stationary phase and is caused by depleted nutrients. The cells reduce their metabolic activity and consume non-essential cellular proteins.
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Tetrazepam is an unusual benzodiazepine in its molecular structure as it has cyclohexenyl group which has substituted the typical 5-phenyl moiety seen in other benzodiazepines. Tetrazepam, is rapidly absorbed after oral administration, within 45 mins and reaches peak plasma levels in less than 2 hours. It is classed as an intermediate acting benzodiazepine with an elimination half-life of approximately 15 hours. It is primarily metabolised to the inactive metabolites 3-hydroxy-tetrazepam and norhydroxytetrazepam.
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Also like cyclosporin, it has a wide range of interactions. Tacrolimus is primarily metabolised by the cytochrome P450 system of liver enzymes, and there are many substances that interact with this system and induce or inhibit the system's metabolic activity. Interactions include that with grapefruit which increases tacrolimus plasma concentrations. As infections are a major cause of morbidity and mortality in the post- transplant patient, the most commonly reported interactions include interactions with anti-microbial drugs.
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However, combining the therapy with chemotherapeutic treatments can help to solve this problem. Another strategy is to use anaerobic bacteria that have been transformed with an enzyme that can convert a non-toxic prodrug into a toxic drug. With the proliferation of the bacteria in the necrotic and hypoxic areas of the tumor, the enzyme is expressed solely in the tumor. Thus, a systemically applied prodrug is metabolised to the toxic drug only in the tumor.
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U.S. safety officials recalled about 4.2 million of the toys. The toy was supposed to contain the non-toxic plasticiser 1,5-pentanediol, but instead contained toxic 1,4-butanediol, which is metabolised into the sedative-hypnotic drug gamma-hydroxybutyric acid. At the time the substitution was discovered, the non-toxic ingredient was three to seven times more expensive than the toxic one. The affected children had seizure-like activity, which is an occasional side-effect of severe GHB overdose.
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RilmazafoneDE Patent 2725164 (リスミー, Rhythmy, previously known as 450191-S) is a water-soluble benzodiazepine prodrug developed in Japan. It has sedative and hypnotic effects. Rilmazafone induces impairment of motor function and has hypnotic properties. Rilmazafone has no effects on benzodiazepine receptors itself, but once inside the body is metabolised by aminopeptidase enzymes in the small intestine to form the active benzodiazepine 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a][1,4]benzodiazepine-2-carboxamide.
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Synapses are specialised minute gaps between neurons. The electrical impulses arriving at the axon terminal triggers the release of packets of chemical messengers (neurotransmitters), which diffuse across the synaptic cleft to receptors on the adjacent dendrite temporarily affecting the likelihood that an electrical impulse will be triggered in the latter neuron. Once released the neurotransmitter is rapidly metabolised or is pumped pack into a neuron. Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum.
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Similar to other benzodiazepines clotiazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant and muscle relaxant pharmacological properties. Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam. Clotiazepam has a short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation.
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Very little is known about the metabolism of cerberin. For the related digoxin, another cardiac glycoside, it is in largest part excreted unchanged by the kidneys (60-80%), with the remaining mostly metabolised by the liver. The half-life for digoxin is 36–48 hours for people with a normal renal function and up to 6 days for people with a compromised renal function. This makes the renal function an important factor in the toxicity of digoxin and perhaps for cerberin as well.
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Acetonitrile has only modest toxicity in small doses. It can be metabolised to produce hydrogen cyanide, which is the source of the observed toxic effects. Generally the onset of toxic effects is delayed, due to the time required for the body to metabolize acetonitrile to cyanide (generally about 2–12 hours). Cases of acetonitrile poisoning in humans (or, to be more specific, of cyanide poisoning after exposure to acetonitrile) are rare but not unknown, by inhalation, ingestion and (possibly) by skin absorption.
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Mean distribution half-life was 0.09 hours and mean elimination half-life was 1.4 hours in paediatric studies. Biodistribution of 14C-labelled docetaxel in three patients showed the bulk of the drug to be metabolised and excreted in bile to the faeces. Of the radioactively labelled docetaxel administered, 80% was eliminated to the faeces with 5% in the urine over seven days, an indication that urinary excretion of docetaxel is minimal. Saliva contributed minimal excretion and no excretion was detected through pulmonary means.
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There are no certain interactions with other drugs. The blood plasma levels of simvastatin were reduced by 57% after a single dose of tocilizumab, but it is not known whether this is clinically relevant. A possible mechanism is that the elevated IL-6 levels of patients with RA suppress the biosynthesis of various cytochrome P450 enzymes, notably CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Tocilizumab lowers IL-6 and thus normalises cytochrome levels, increasing the metabolization of simvastatin (and possibly other cytochrome metabolised drugs).
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After local application, only traces of adrenalone are found in the blood, which is partly a consequence of the vasoconstriction caused by the drug via alpha-1 adrenergic receptors. In an (unspecified) pharmacological model, hypertensive (blood pressure increasing) action has been found to be about 0.5% that of epinephrine at equivalent plasma concentrations. Therefore, systemic effects are unlikely. Like epinephrine, adrenalone is metabolised by catechol-O-methyl transferase (COMT), yielding 3O-methyladrenalone, which in turn is N-demethylized by monoamine oxidase (MAO).
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Death is normally due to ventricular arrhythmias, progressive hypotension unresponsive to treatment, and aspiration pneumonitis. Symptoms in domestic animals vary: dogs tend to show nervous system signs such as convulsions, vocalization, and uncontrollable running, whilst large herbivores such as cattle and sheep more predominantly show cardiac signs. Sub-lethal doses of sodium fluoroacetate may cause damage to tissues with high energy needs — in particular, the brain, gonads, heart, lungs, and fetus. Sub- lethal doses are typically completely metabolised and excreted within four days.
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If drug use is believed to have occurred in relation to an accident or incident and there is not sufficient time to conduct an investigation before the drug in use could be metabolised within the body such that its use could not be detected, Commanding Officer's are authorized to order a test. The focus of the policy is on discerning all factors that caused an incident and promoting safety; the results from a urine test cannot be used at disciplinary proceedings.
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In enzymology, a creatininase () is an enzyme that catalyses the hydrolysis of creatinine to creatine, which can then be metabolised to urea and sarcosine by creatinase. :creatinine + H2O \rightleftharpoons creatine Thus, the two substrates of this enzyme are creatinine and H2O, whereas its product is creatine. Creatininase is a member of the urease-related amidohydrolases, the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in cyclic amides. The systematic name of this enzyme class is creatinine amidohydrolase.
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Most of erythromycin is metabolised by demethylation in the liver by the hepatic enzyme CYP3A4. Its main elimination route is in the bile with little renal excretion, 2%-15% unchanged drug. Erythromycin's elimination half-life ranges between 1.5 and 2.0 hours and is between 5 and 6 hours in patients with end-stage renal disease. Erythromycin levels peak in the serum 4 hours after dosing; ethylsuccinate peaks 0.5-2.5 hours after dosing, but can be delayed if digested with food.
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Less than 1 percent of the drug is excreted unchanged; 92 percent of the metabolised drug is excreted within the first 12 hours. The main metabolites are the N-oxide Ro 12-5637 formed via morpholine N-oxidation and lactam derivative Ro 12-8095 formed via morpholine C-oxidation; active metabolites are found only in trace amounts. The unchanged drug (less than 1%) as well as the metabolites are excreted renally (in urine). The main degradation pathway of moclobemide is oxidation.
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The substance is metabolised by the liver enzyme CYP3A4. In a study, the strong CYP3A4 inhibitor ketoconazole increased the maximal blood plasma concentrations of lercanidipine by a factor of eight, and the area under the curve by a factor of 15. In another study, ciclosporin increased lercanidipine plasma levels threefold when given at the same time. Other inhibitors of this enzyme, such as itraconazole, erythromycin, and grapefruit juice, are also expected to increase plasma concentrations and thus amplify the antihypertensive effect.
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The degree of the effect varies widely between individuals and between samples of juice, and therefore cannot be accounted for a priori. Another mechanism of interaction is possibly through the MDR1 (multidrug resistance protein 1) that is localized in the apical brush border of the enterocytes. P-glycoprotein (Pgp) transports lipophilic molecules out of the enterocyte back into the intestinal lumen. Drugs that possess lipophilic properties are either metabolised by CYP3A4 or removed into the intestine by the Pgp transporter.
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Inversely, dextromethorphan, a cough suppressor, is best taken orally because it needs to be metabolised by the liver into dextrorphan in order to be effective. This latter principle is that of most prodrugs. The use of suppositories is a way to bypass partially the portal vein: the upper 1/3 of the rectum is drained into the portal vein while the lower 2/3 are drained into the internal iliac vein that goes directly in the inferior vena cava (thus bypassing the liver).
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A 20-ml ampoule of 1% propofol emulsion, as sold in Australia by alt=Large vial filled with milky white fluid Propofol is highly protein-bound in vivo and is metabolised by conjugation in the liver. The half-life of elimination of propofol has been estimated to be between 2 and 24 hours. However, its duration of clinical effect is much shorter, because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, a single dose of propofol typically wears off within minutes.
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Their discoveries were the result of the first organized team effort to optimize the biological activity of a lead compound through systematic chemical modifications. This scheme is the basis for most modern pharmaceutical research. Both salvarsan and neosalvarsan are prodrugs — that is, they are metabolised into the active drug in the body. Although, like salvarsan, it was originally believed to contain an arsenic-arsenic double bond, this is now known to be incorrect, and exists as a mixture of differently sized rings with arsenic-arsenic single bonds.
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Polyprenols are similar to compounds found in the cells of humans and animals known as dolichols. Research indicates that ingested polyprenols are metabolised by human and animal liver into dolichols which then take part in the dolichol phosphate cycle, which is why Bioeffectives are so easily assimilated by humans and animals, and have such high efficacy and low toxicity. The isolation of Bioeffectives involves patented extraction technology. The process uses a soft extraction procedure that enables the polyprenols to be extracted without destroying their biologically-active properties.
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Inhibitors of the liver enzyme CYP3A4, such as ketoconazole and possibly grapefruit juice, increase blood plasma levels of ticagrelor and consequently can lead to bleeding and other adverse effects. Ticagrelor is a weak CYP3A4 inhibitor and is known to increase the concentrations of CYP3A4 metabolised medications, however this interaction is unlikely to be clinically significant for atorvastatin and simvastatin at recommended doses. CYP3A4 inducers, for example rifampicin and possibly St. John's wort, can reduce the effectiveness of ticagrelor. There is no evidence for interactions via CYP2C9.
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In ABT-770 the two phenyl rings are directly connected but in Prinomastat the two phenyl rings are connected by an oxygen atom, forming a diphenylether. These three permutations direct the SAR away from MMP-1 and toward the „deep pocket“ MMPs such as the gelatinases. ABT-770 shows anticancer activity in animal models, but it is easily metabolised to an amine metabolite that causes phospholipidosis. MMI-166 has shown anticancer activity in numerous animal models, but there is no data available of its clinical performance.
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Benzoic acid is metabolised to either benzoyl glucuronide or hippuric acid. Benzoyl glucuronide is produced by the reaction of benzoic acid with glucuronic acid, which accounts for 10–20% of benzoic acid elimination. Hippuric acid is also known as benzoylglycine and is produced from benzoic acid in two steps: first benzoic acid is converted to benzoyl-CoA by the enzyme benzoyl-CoA synthase; then benzoyl-CoA is converted to hippuric acid by benzoyl-CoA:glycine N-acyltransferase. Hippuric acid is the primary urinary metabolite of toluene.
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Elvitegravir is metabolised via the liver enzyme CYP3A. Substances that induce this enzyme can reduce elvitegravir concentrations in the body, potentially triggering the development of resistant virus strains. Consequently, co-administration of strong CYP3A inducers is contraindicated; examples are rifampicin, the anticonvulsants carbamazepine, phenobarbital and phenytoin, as well as St John's wort. Glucuronidation of elvitegravir is facilitated by the enzymes UGT1A1 and 3, resulting in increased blood plasma levels when taken together with strong UGT1A inhibitors such as ritonavir and other HIV protease inhibitors.
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Isomaltulose is an available carbohydrate like sucrose and most other sugars or maltodextrins, in the sense that it is fully metabolised in the small intestine, and does not enter the large intestine or get excreted in urine. When eaten by humans, isomaltulose is digested completely and absorbed. Its intestinal digestion involves the enzyme isomaltase, which is located at the surface of the brush border lining the inner wall of the small intestine. This enzyme is otherwise involved in the digestion of α-1,6 linkages present in starch.
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The TCAs are highly metabolised by the cytochrome P450 (CYP) hepatic enzymes. Drugs that inhibit cytochrome P450 (for example cimetidine, methylphenidate, fluoxetine, antipsychotics, and calcium channel blockers) may produce decreases in the TCAs' metabolism, leading to increases in their blood concentrations and accompanying toxicity. The major factor that distinguishes SSRI's amongst one another is the inhibition of select CYP enzymes . Drugs that prolong the QT interval including antiarrhythmics such as quinidine, the antihistamines astemizole and terfenadine, and some antipsychotics may increase the chance of ventricular dysrhythmias.
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It inhibits cell division, promotes seed maturation, and dormancy, and promotes stomatal closure. It was so named because it was originally thought to control abscission. Ethylene is a gaseous hormone that is produced in all higher plant tissues from methionine. It is now known to be the hormone that stimulates or regulates fruit ripening and abscission, and it, or the synthetic growth regulator ethephon which is rapidly metabolised to produce ethylene, are used on industrial scale to promote ripening of cotton, pineapples and other climacteric crops.
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8-Phenyltheophylline (8-phenyl-1,3-dimethylxanthine, 8-PT) is a drug derived from the xanthine family which acts as a potent and selective antagonist for the adenosine receptors A1 and A2A, but unlike other xanthine derivatives has virtually no activity as a phosphodiesterase inhibitor. It has stimulant effects in animals with similar potency to caffeine. Coincidentally 8-phenyltheophylline has also been found to be a potent and selective inhibitor of the liver enzyme CYP1A2 which makes it likely to cause interactions with other drugs which are normally metabolised by CYP1A2.
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First, methanol can be fatal due to effects on the central nervous system, acting as a central nervous system depressant in the same manner as ethanol poisoning. Second, in a process of toxication, it is metabolised to formic acid (which is present as the formate ion) via formaldehyde in a process initiated by the enzyme alcohol dehydrogenase in the liver. Methanol is converted to formaldehyde via alcohol dehydrogenase (ADH) and formaldehyde is converted to formic acid (formate) via aldehyde dehydrogenase (ALDH). The conversion to formate via ALDH proceeds completely, with no detectable formaldehyde remaining.
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Ecgonidine (anhydroecgonine) is an alkaloid related to ecgonine and cocaine. It has a structure with a cycloheptene ring, with a nitrogen bridge, and a carboxylic acid side chain. Methylecgonidine is produced by pyrolysis in the process of smoking crack cocaine, and then subsequently metabolised to ecgonidine, and so these two compounds can be tested for as a specific biomarker for crack cocaine use. Ecgonidine is formed as a metabolite of methylecgonidine, and so the relative concentrations of the two compounds can be used to gauge how recently crack cocaine was smoked.
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The combined concentrations of gases in any given tissue depend on the history of pressure and gas composition. Under equilibrium conditions, the total concentration of dissolved gases is less than the ambient pressure—as oxygen is metabolised in the tissues, and the carbon dioxide produced is much more soluble. However, during a reduction in ambient pressure, the rate of pressure reduction may exceed the rate at which gas is eliminated by diffusion and perfusion. If the concentration gets too high, it may reach a stage where bubble formation can occur in the supersaturated tissues.
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In the United States, it was never available and is classified as a Schedule I drug with a DEA ACSCN of 9301. The salts in use are the bitartrate (free base conversion ratio 0.643) and hydrochloride (0.770). The 2014 national aggregate manufacturing quota was 2 grams, unchanged from prior years. Hydromorphinol is metabolised mainly in the liver in the same fashion as many other opioids and is itself a minor active metabolite of 14-Hydroxydihydrocodeine, an uncommonly used opiate (but is therefore also an active metabolite of a first-order active metabolite of oxycodone).
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Although ACT-132577 has a lower affinity for the ET receptors than its parent compound, It maintains higher plasma concentrations than macitentan. Both compounds can be excreted from the body through the urine or feces. Co-administration of ciclosporin has only a slight effect on the concentrations of macitentan and its active metabolite, while rifampicin decreases the area under the curve (AUC) of the drug's blood plasma concentration by 79%, and ketoconazole approximately doubles it. This corresponds to the finding that macitentan is mainly metabolised via the liver enzyme CYP3A4.
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The peptide tumor-associated trypsin inhibitor (TATI) has been used as a marker of mucinous ovarian carcinoma, urothelial carcinoma, and renal cell carcinoma. TATI is metabolised by the kidneys and is, thus, elevated in patients with kidney failure. It may be elevated in non-neoplastic processes such as pancreatitis and can be used as a prognostic marker in this setting (levels above 70 micrograms/L are associated with poor prognosis). Fifty percent of stage I mucinous ovarian carcinomas are associated with elevated TATI, and nearly 100% of stage IV tumors show elevated TATI.
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This process is impaired in all subtypes of hepatic encephalopathy, either because the hepatocytes (liver cells) are incapable of metabolising the waste products or because portal venous blood bypasses the liver through collateral circulation or a medically constructed shunt. Nitrogenous waste products accumulate in the systemic circulation (hence the older term "portosystemic encephalopathy"). The most important waste product is ammonia (NH3). This small molecule crosses the blood–brain barrier and is absorbed and metabolised by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex.
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The primary use of the chemoton model is in the study of the chemical origin of life. Because chemoton itself can be, though in theory, as a primitive or minimal cellular life as it satisfies the definition of what a cell is (that it is a unit of biological activity enclosed by a membrane and capable of self-reproduction). Experimental demonstration showed that a synthesised chemotron can survive in a wide range of chemical solutions, it formed materials for its internal components, it metabolised its chemicals, and it grew in size and multiplied itself.
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While increase of dopamine levels is a desired interaction, tolcapone can theoretically also increase the levels of other drugs metabolised by COMT, such as the AADC inhibitors carbidopa and benzerazide, as well as methyldopa, dobutamine, apomorphine, adrenaline, and isoprenaline. In studies, a slight interaction with benzerazide was seen, but not with carbidopa. Other interactions with this group of drugs have not been studied. A related type of theoretical interactions is with drugs that increase catecholamine concentrations, such as monoamine oxidase (MAO) inhibitors and noradrenaline reuptake inhibitors; these also showed only slight effects in practice.
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Fluconazole is an inhibitor of the human cytochrome P450 system, particularly the isozyme CYP2C19 (CYP3A4 and CYP2C9 to lesser extent) In theory, therefore, fluconazole decreases the metabolism and increases the concentration of any drug metabolised by these enzymes. In addition, its potential effect on QT interval increases the risk of cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval. Berberine has been shown to exert synergistic effects with fluconazole even in drug-resistant Candida albicans infections. Fluconazole may increase the serum concentration of Erythromycin (Risk X: avoid combination).
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One study estimated, on average, detectable cancer develops ten years from the start of daily aristolochic acid consumption. A patient thought to have AAN can be confirmed through phytochemical analysis of plant products consumed and detection of aristolactam DNA adducts in the renal cells. (Aristolochic acid is metabolised into aristolactam.) Additionally, mutated proteins in renal cancers as a result of transversion of A:T pairings to T:A are characteristically seen in aristolochic acid-induced mutations. In some cases, early detection resulting in cessation of aristolochia-product consumption can lead to reverse of the kidney damage.
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The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. 80% of MDMA is metabolised in the liver, and about 20% is excreted unchanged in the urine. MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The metabolism may be primarily by cytochrome P450 (CYP450) enzymes CYP2D6 and CYP3A4 and COMT.
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Sinalbin is a glucosinolate found in the seeds of white mustard, Sinapis alba, and in many wild plant species. In contrast to mustard from black mustard (Brassica nigra) seeds which contain sinigrin, mustard from white mustard seeds has only a weakly pungent taste. RICHARD H. Arômes alimentaires Document de cours Sinalbin is metabolised to form the mustard oil 4-hydroxybenzyl isothiocyanate by the enzyme myrosinase. The less sharp taste of white mustard is because 4-hydroxybenzyl isothiocyanate is unstable and degrades to 4-hydroxybenzyl alcohol and a thiocyanate ion, which are not pungent.
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Inorganic arsenic and its compounds, upon entering the food chain, are progressively metabolised (detoxified) through a process of methylation. The methylation occurs through alternating reductive and oxidative methylation reactions, that is, reduction of pentavalent to trivalent arsenic followed by addition of a methyl group (CH3). Cacodylic acid, formed in the liver after ingestion of arsenic. In mammals, methylation occurs in the liver by methyltransferases, the products being the (CH3)2AsOH (dimethylarsinous acid) and (CH3)2As(O)OH (dimethylarsinic acid), which have the oxidation states As(III) and As(V), respectively.
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Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. The lysine/diaminopimelic acid branch of the aspartate pathway produces the essential amino acid lysine via the intermediate meso- diaminopimelic acid (meso-DAP), which is also a vital cell wall component in Gram-negative bacteria. The production of dihydropicolinate from aspartate- semialdehyde controls flux into the lysine/diaminopimelic acid pathway. Three variants of this pathway exist, differing in how tetrahydropicolinate (formed by reduction of dihydropicolinate) is metabolised to meso-DAP.
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Succinylcholine interacts with nicotinic receptor to open the channel and cause depolarization of the end plate, which later spread to and result in depolarization of adjacent membranes. As a result, there is disorganisation of contraction of muscle motor unit. Later, since succinylcholine is not able to be metabolised and removed effectively at the synapse, the depolarized membranes remain in state of depolarisation and cannot respond to additional impulses. Phase I blok effect can be increased by cholinesterase inhibitors which further delay the action of metabolism and removal by cholinesterase.
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Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in urine samples alongside noscapine include papaverine and acetylcodeine. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine. Detection is performed by gas chromatography-mass spectrometry or liquid chromatography- mass spectrometry (LCMS) but can also use a variety of other analytical techniques.
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After oral administration, abiraterone acetate, the prodrug form in the commercial preparation, is converted into the active form, abiraterone. This conversion is likely to be esterase-mediated and not CYP- mediated. Administration with food increases absorption of the drug and thus has the potential to result in increased and highly variable exposures; the drug should be consumed on an empty stomach at least one hour before or two hours after food. The drug is highly protein bound (>99%), and is metabolised in the liver by CYP3A4 and SULT2A1 to inactive metabolites.
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Due to its activity on oestrogen receptors, red clover is contraindicated in people with a history of breast cancer, endometriosis, ovarian cancer, uterine cancer, uterine fibroids or other oestrogen-sensitive conditions, although some authors have suggested the high isoflavone content counteracts this, and even provides benefits in these conditions. It is said to be a blood cleanser. Due to its coumarin derivatives, T. pratense should be used with caution in individuals with coagulation disorders or currently undergoing anticoagulation therapy. It is metabolised by CYP3A4 and therefore caution should be used when taking it with other drugs using this metabolic pathway.
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In addition it is odourless or pleasant to inhale; safe for all ages and in pregnancy; not metabolised; rapid in onset and offset; potent; and safe for exposure to operating room staff. It is also cheap to manufacture; easy to transport and store, with a long shelf life; easy to administer and monitor with existing equipment; stable to light, plastics, metals, rubber and soda lime; non-flammable and environmentally safe. None of the agents currently in use are ideal, although many have some of the desirable characteristics. For example, sevoflurane is pleasant to inhale and is rapid in onset and offset.
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Like all potent inhalation anaesthetic agents it is a known trigger of malignant hyperthermia. Like the other potent inhalation agents it relaxes the uterus in pregnant women which is associated with more blood loss at delivery or other procedures on the gravid uterus. The obsolete (as an anaesthetic) agent methoxyflurane had a nephrotoxic effect and caused acute kidney injury, usually attributed to the liberation of fluoride ions from its metabolism. Enflurane is similarly metabolised but the liberation of fluoride results in a lower plasma level and enflurane related kidney failure seemed unusual if seen at all.
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Organisms are said to be susceptible to nitrofurantoin if their minimum inhibitory concentration is 32 μg/ml or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg is less than 1 μg/ml and may be undetectable. Its bioavailability is about 90% and the urinary excretion is 40%Antibiot. Chemother. 1978, 25, 233–252 tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more.
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Fluparoxan was not metabolised by human cytochrome P450 enzymes CYP 1A and CYP 2A, and was found not to be a mutagen in cultured human peripheral lymphocytes and did not cause gene mutation when administered to Chinese hamster fibroblasts in culture. No mutagenic potential was identified in microbiological mutagenicity tests including a fluctuation test with S9 activation. No hydroxylated metabolites were identified after incubation with rat liver microsomes (S9) or in rat urine following oral dosing. The compound was well tolerated on repeat oral administration to rat (≤ 200 mg /kg/day) and dog (≤ 80 mg/kg/day) for 12 months.
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Its use is advised against in people on strong CYP3A4 inhibitors such as clarithromycin, chloramphenicol, ketoconazole, ritonavir and nefazodone due to its reliance on CYP3A4 for metabolism. Likewise it is a CYP3A4, CYP2D6 and CYP2C9 inhibitor and hence concurrent treatment with substrates of any of these enzymes may increase plasma concentrations of said drugs. Since imatinib is mainly metabolised via the liver enzyme CYP3A4, substances influencing the activity of this enzyme change the plasma concentration of the drug. An example of a drug that increases imatinib activity and therefore side effects by blocking CYP3A4 is ketoconazole.
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Conversely, urine concentrations of free light chains could increase if renal function improved in a multiple myeloma patient receiving treatment. This could account for the poor correlation frequently seen when urine and serum free light-chain concentrations are compared. The 500 mg of FLCs produced per day by the normal lymphoid system, however, flows through the glomeruli and is completely processed by the proximal tubules. If the proximal tubules of the nephrons are damaged or stressed (such as in hard exercise), filtered FLCs may not be completely metabolised and small amounts may then appear in the urine.
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It used to be thought that sucrose and starch are metabolised in similar ways, and so are interchangeable from the nutritional point of view, but more recent evidence had shown that their metabolism is significantly different. The need for carbohydrate as a component of the diet can be entirely satisfied by starch (often in the form of bread or pasta), which is broken down in the body to glucose. On the other hand sucrose, which is broken down to equal quantities of glucose and fructose, is not an essential dietary component even in small amounts.For there being "no physiological requirement for sugar", see .
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Since there is evidence that oxygen plays a part in the narcotic effects of a gas mixture, the NOAA diving manual recommends treating oxygen and nitrogen as equally narcotic. This is now preferred to the previous method of considering only nitrogen as narcotic, since it is more conservative. In this analysis, it is assumed that the narcotic potentials of nitrogen and oxygen are similar. Although oxygen has greater lipid solubility than nitrogen and therefore should be more narcotic (Meyer-Overton correlation), it is likely that some of the oxygen is metabolised, thus reducing its effect to a level similar to that of nitrogen.
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MexazolamDE Patent 1954065 (marketed under the trade names Melex and Sedoxil) is a drug which is a benzodiazepine derivative. Mexazolam has been trialed for anxiety and was found to be effective in alleviating anxiety at one week follow-up, however, after three weeks of therapy mexazolam had lost its therapeutic anxiolytic properties becoming no more effective than placebo, presumably due to benzodiazepine tolerance. Mexazolam is metabolised via the CYP3A4 pathway. HMG-CoA reductase inhibitors including simvastatin, simvastatin acid, lovastatin, fluvastatin, atorvastatin and cerivastatin inhibit the metabolism of mexazolam, but not the HMG-CoA reductase inhibitor pravastatin.
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Research indicates that ingested polyprenols are metabolised by human and animal liver into dolichols which then take part in the dolichol phosphate cycle and are therefore easily assimilated by humans and animals. The pharmacological activity of polyprenols is based on their substitutive effect in the case of dolichol deficits which are observed with chronic inflammatory, degenerative and oncological diseases.. Live conifer needles are one of the richest and most widely available sources for polyprenol extraction in the world. Commercial extraction of polyprenols involves a soft extraction procedure that enables them to be extracted without destroying their biological activity..
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Data on the metabolism of CoQ10 in animals and humans are limited. A study with 14C-labeled CoQ10 in rats showed most of the radioactivity in the liver two hours after oral administration when the peak plasma radioactivity was observed, but CoQ9 (with only 9 isoprenyl units) is the predominant form of coenzyme Q in rats. It appears that CoQ10 is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ10 supplementation, the levels return to normal within a few days, irrespective of the type of formulation used.
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Latanoprost is absorbed well through the cornea and completely hydrolysed to the active latanoprost acid. Highest concentrations of the acid in the aqueous humour are reached two hours after application, lowering of intraocular pressure starts after 3 to 4 hours, the highest effect is found after 8 to 12 hours, and its action lasts at least 24 hours. When latanoprost acid reaches the circulation, it is quickly metabolised in the liver by beta oxidation to 1,2-dinor- and 1,2,3,4-tetranor-latanoprost acid; blood plasma half life is only 17 minutes. The metabolites are mainly excreted via the kidney.
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Once at a healthcare facility, support must be provided until the venom is metabolised and the victim can breathe unaided, especially if no species-specific antivenom is available. Given that the toxins alter acetylcholine transmission which causes the paralysis, some patients have been successfully treated with cholinesterase inhibitors, such as physostigmine or neostigmine, but success is variable and may be species-dependent, as well. If death occurs, it typically takes place about 6-12 hours after the krait bite, but can be significantly delayed. Cause of death is usually respiratory failure—suffocation by complete paralysis of the diaphragm.
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Insulin in turn stimulates the uptake of large neutral branched-chain amino acids (BCAA), but not tryptophan, into muscle, increasing the ratio of tryptophan to BCAA in the blood stream. The resulting increased tryptophan ratio reduces competition at the large neutral amino acid transporter (which transports both BCAA and aromatic amino acids), resulting in more uptake of tryptophan across the blood–brain barrier into the cerebrospinal fluid (CSF). Once in the CSF, tryptophan is converted into serotonin in the raphe nuclei by the normal enzymatic pathway. The resultant serotonin is further metabolised into melatonin by the pineal gland.
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The urea in wines results from the metabolism of arginine or citrulline by yeast or other organisms. The urea waste product is initially metabolised inside the yeast cell until it builds up to a certain level. At that point, it is excreted externally where it is able to react with the alcohol to create ethyl carbamate. In 1988, wine and other alcoholic beverage manufacturers in the United States agreed to control the level of ethyl carbamate in wine to less than 15 ppb (parts per billion), and in stronger alcoholic drinks to less than 125 ppb.
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However, the active metabolite of midazolam is minor and contributes to only 10 percent of biological activity of midazolam. Midazolam is poorly absorbed orally, with only 50 percent of the drug reaching the bloodstream. Midazolam is metabolised by cytochrome P450 (CYP) enzymes and by glucuronide conjugation. The therapeutic as well as adverse effects of midazolam are due to its effects on the GABA receptors; midazolam does not activate GABA receptors directly but, as with other benzodiazepines, it enhances the effect of the neurotransmitter GABA on the GABA receptors (↑ frequency of Cl channel opening) resulting in neural inhibition.
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The commercial SABAs, salbutamol and terbutaline are resistant to COMT but are slowly metabolised by MAO, while the LABAs are resistant to both COMT and MAO. Also, the long duration of action for salmeterol is related to increased lipophilicity of the molecules, allowing it to remain for a longer time in the lungs. β2-agonists are mainly eliminated by the renal process after parenteral administration, while after oral administration a more pronounced metabolic clearance (high first pass effect) is responsible for a low bioavailability. The elimination after inhalation has not been studied but the profile is likely somewhere between what we see after parenteral and oral administration.
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Rapid increase in metabolism is needed during activation of T lymphocytes, which reside in peripheral blood containing stable concentrations of glucose. As glucose is plentiful, T-cells are able to switch to fast utilization of glucose using the coreceptor CD28.. This CD3/CD28 signaling parallels insulin signaling, as both lead to higher expression of glucose transporter 1 (Glut-1) on the cell surface via the activation of Akt kinase. CD28 signal transduction not only leads to higher glucose uptake but also to an increased rate of glycolysis. Most of glucose taken by activated T lymphocytes is metabolised to lactate and dumped out of the cells.
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The action of cathine and cathinone on the reuptake of epinephrine and norepinephrine has been demonstrated in lab animals, showing that one or both of these chemicals cause(s) the body to recycle these neurotransmitters more slowly, resulting in the wakefulness and insomnia associated with khat use. Receptors for serotonin show a high affinity for cathinone, suggesting this chemical is responsible for feelings of euphoria associated with chewing khat. In mice, cathinone produces the same types of nervous pacing or repetitive scratching behaviours associated with amphetamines. The effects of cathinone peak after 15 to 30 minutes, with nearly 98% of the substance metabolised into norephedrine by the liver.
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In addition to reversibility, MAOIs differ by their selectivity of the MAO enzyme subtype. Some MAOIs inhibit both MAO-A and MAO-B equally, other MAOIs have been developed to target one over the other. MAO-A inhibition reduces the breakdown of primarily serotonin, norepinephrine, and dopamine; selective inhibition of MAO-A allows for tyramine to be metabolised via MAO-B. Agents that act on serotonin if taken with another serotonin-enhancing agent may result in a potentially fatal interaction called serotonin syndrome or with irreversible and unselective inhibitors (such as older MAOIs), of MAO a hypertensive crisis as a result of tyramine food interactions is particularly problematic with older MAOIs.
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Retinyl palmitate has been used in skin creams, where it is broken down to retinol and ostensibly metabolised to retinoic acid, which has potent biological activity, as described above. The retinoids (for example, 13-cis-retinoic acid) constitute a class of chemical compounds chemically related to retinoic acid, and are used in medicine to modulate gene functions in place of this compound. Like retinoic acid, the related compounds do not have full vitamin A activity, but do have powerful effects on gene expression and epithelial cell differentiation.American Cancer Society: Retinoid Therapy Pharmaceutics utilizing megadoses of naturally occurring retinoic acid derivatives are currently in use for cancer, HIV, and dermatological purposes.
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This suggests that the various acyltransferases present in mammalian and yeast cells may be responsible for producing different pools of PA. The conversion of PA into diacylglycerol (DAG) by LPPs is the commitment step for the production of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). In addition, DAG is also converted into CDP-DAG, which is a precursor for phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphoinositides (PIP, PIP2, PIP3). PA concentrations are maintained at extremely low levels in the cell by the activity of potent LPPs. These convert PA into DAG very rapidly and, because DAG is the precursor for so many other lipids, it too is soon metabolised into other membrane lipids.
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While a significant amount of toluene, 25%–40%, is exhaled unchanged via the lungs, a greater proportion is metabolised and excreted via other pathways. The primary route of toluene metabolism is by hydroxylation to benzyl alcohol by members of the cytochrome P450 (CYP) superfamily. There are five CYPs which are important in toluene metabolism, CYP1A2, CYP2B6, CYP2E1, CYP2C8, and CYP1A1. The first four seem to be involved in the hydroxylation of toluene to benzyl alcohol. CYP2E1 seems to be the primary enzyme in the hydroxylation of toluene, accounting for roughly 44% of toluene metabolism; however, there is a great deal of ethnic variability, in the Finnish population for example the primary enzyme is CYP2B6.
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Ester local anesthetics (such as procaine, amethocaine, cocaine, benzocaine, tetracaine) are generally unstable in solution and fast-acting, are rapidly metabolised by cholinesterases in the blood plasma and liver, and more commonly induce allergic reactions. Amide local anesthetics (such as lidocaine, prilocaine, bupivicaine, levobupivacaine, ropivacaine, mepivacaine, dibucaine and etidocaine) are generally heat-stable, with a long shelf life (around two years). Amides have a slower onset and longer half-life than ester anesthetics, and are usually racemic mixtures, with the exception of levobupivacaine (which is S(-) -bupivacaine) and ropivacaine (S(-)-ropivacaine). Amides are generally used within regional and epidural or spinal techniques, due to their longer duration of action, which provides adequate analgesia for surgery, labor, and symptomatic relief.
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The major safety hazards of nitrous oxide come from the fact that it is a compressed liquefied gas, an asphyxiation risk and a dissociative anaesthetic. While relatively non-toxic, nitrous oxide has a number of recognised ill effects on human health, whether through breathing it in or by contact of the liquid with skin or eyes. Nitrous oxide is a significant occupational hazard for surgeons, dentists and nurses. Because nitrous oxide is minimally metabolised in humans (with a rate of 0.004%), it retains its potency when exhaled into the room by the patient, and can pose an intoxicating and prolonged exposure hazard to the clinic staff if the room is poorly ventilated.
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However, Vela Pharmaceuticals of New Jersey is developing the D-enantiomer (dextofisopam) as a treatment for irritable bowel syndrome, with moderate efficacy demonstrated in clinical trials so far. Tofisopam is also claimed to be a PDE10A inhibitor, which may provide an alternative mechanism of action for its various therapeutic effects, and this action has been proposed to make tofisopam potentially useful as a treatment for schizophrenia.Nielsen EB, Kehler J, Nielsen J, Brøsen P. Use of Tofisopam as a PDE10A inhibitor. WIPO Patent WO/2007/082546 Tofisopam has been shown to act as an inhibitor of the liver enzyme CYP3A4, and this could cause dangerous drug interactions with other medications metabolised by this enzyme, although the clinical significance of these findings remains unclear.
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Methylecgonidine (anhydromethylecgonine; anhydroecgonine methyl ester; AEME) is a chemical intermediate derived from ecgonine or cocaine. Methylecgonidine is a pyrolysis product formed when crack cocaine is smoked, making this substance a useful biomarker to specifically test for use of crack cocaine, as opposed to powder cocaine which does not form methylecgonidine as a metabolite. Methylecgonidine has a relatively short half-life of 18–21 minutes, after which it is metabolised to ecgonidine, meaning that the relative concentrations of the two compounds can be used to estimate how recently crack cocaine has been smoked. Methylecgonidine has been shown to be specifically more harmful to the body than other byproducts of cocaine; for example to the heart,Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate - Scheidweiler et al.
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6-Monoacetylcodeine (6-MAC) is an acetate ester of codeine in which the hydroxyl group on the 6 position has been acetylated. It is occasionally present as an impurity in street heroin and is typically created when attempting to create heroin from a solution of morphine in which some of the codeine from the original opium solution still remains. It is formed either through the addition of acetic anhydride, which can only acetylate the 6 position on the codeine or as a result of the addition of acetic acid with a catalyst in an attempt to create 6-monoacetylmorphine, the equivalent ester of morphine which is slightly more potent than heroin itself. 6-monoacetylcodeine is eventually metabolised into codeine and then into morphine.
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Early observations of locusts showed that despite the fact that lipids are metabolised by flight muscle in order to maintain flight, which would be transported from the haemolymph, there was often still a high concentration of lipids in the haemolymph, implying that an agent may be responsible for activating lipid transport into the haemolymph and this was thought most likely to be hormonal regulation.Chapter Eleven The hormone itself is part of a larger family, often referred to as red pigment concentrating hormones (RPCH) discovered in crustaceans and the typical makeup of hormones in this family includes a length between 8 and 10 amino acids, blocked N and C termini, phenylalanine or tyrosine at position 4 and tryptophan at position 8.
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Under equilibrium conditions, the total concentration of dissolved gases will be less than the ambient pressure, as oxygen is metabolised in the tissues, and the carbon dioxide produced is much more soluble. However, during a reduction in ambient pressure, the rate of pressure reduction may exceed the rate at which gas can be eliminated by diffusion and perfusion, and if the concentration gets too high, it may reach a stage where bubble formation can occur in the supersaturated tissues. When the pressure of gases in a bubble exceed the combined external pressures of ambient pressure and the surface tension from the bubble - liquid interface, the bubbles will grow, and this growth can cause damage to tissues. Symptoms caused by this damage are known as Decompression sickness.
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Previous attempts to produce such fermented protein foodstuffs were thwarted by excessive levels of DNA or RNA; without the heat treatment, purines, found in nucleic acids, are metabolised by humans to produce uric acid, which can lead to gout. The product is dried and mixed with egg albumen, which acts as a binder. It is then textured, giving it some of the grained character of meat, and pressed into a mince resembling ground beef; forms resembling chicken breasts, meatballs, and turkey roasts; or chunks resembling diced chicken breast. In these forms, Quorn has a varying colour and a mild flavour resembling the imitated meat product, and is suitable for use as a replacement for meat in many dishes, such as stews and casseroles.
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This is known as outgassing, and occurs during decompression, when the reduction in ambient pressure or a change of breathing gas reduces the partial pressure of the inert gas in the lungs. The combined concentrations of gases in any given tissue will depend on the history of pressure and gas composition. Under equilibrium conditions, the total concentration of dissolved gases will be less than the ambient pressure, as oxygen is metabolised in the tissues, and the carbon dioxide produced is much more soluble. However, during a reduction in ambient pressure, the rate of pressure reduction may exceed the rate at which gas can be eliminated by diffusion and perfusion, and if the concentration gets too high, it may reach a stage where bubble formation can occur in the supersaturated tissues.
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The combined concentrations of gases in any given tissue will depend on the history of pressure and gas composition. Under equilibrium conditions, the total concentration of dissolved gases will be less than the ambient pressure, as oxygen is metabolised in the tissues, and the carbon dioxide produced is much more soluble. However, during a reduction in ambient pressure, the rate of pressure reduction may exceed the rate at which gas can be eliminated by diffusion and perfusion, and if the concentration gets too high, it may reach a stage where bubble formation can occur in the supersaturated tissues. When the pressure of gases in a bubble exceed the combined external pressures of ambient pressure and the surface tension from the bubble - liquid interface, the bubbles will grow, and this growth can cause damage to tissues.
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A slow and gradual withdrawal customised to the individual and, if indicated, psychological support is the most effective way of managing the withdrawal. Opinion as to the time needed to complete withdrawal ranges from four weeks to several years. A goal of less than six months has been suggested, but due to factors such as dosage and type of benzodiazepine, reasons for prescription, lifestyle, personality, environmental stresses, and amount of available support, a year or more may be needed to withdraw. Withdrawal is best managed by transferring the physically dependent patient to an equivalent dose of diazepam because it has the longest half-life of all of the benzodiazepines, is metabolised into long-acting active metabolites and is available in low- potency tablets, which can be quartered for smaller doses.
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These acylation reactions may sequester and thereby inactivate or store the metabolites for release during cell stimulation. 12(S)-HETE and 12(R)-HETE are converted to 12-oxo-ETE by microsomal NAD+-dependent 12-hydroxyeicosanoid dehydrogenase in porcine polymophonuclear leukocytes; a similar pathway may be active in rabbit corneal epithelium, cow corneal epithelium, and mouse keratinocytes although this pathway has not been described in human tissues. 12-oxo-ETE is metabolised by cytosolic NADH-dependent 12-oxoeicosinoid Δ10-reductase to 12-oxo-5Z,8Z,14Z-eicosatrienoic acid (12-oxo-ETrE); 12-ketoreductase may then reduce this 12-oxo-ETrE to 12(R)-hydroxy-5Z,8Z,14Z-eicosatrienoic acid (12(R)-HETrE) and to a lesser extent 12(S)-hydroxy-5Z,8Z,14Z-eicosatrienoic acid (12(S)-HETrE).
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Oxcarbazepine, licarbazepine and many other common drugs influence each other through interaction with the Cytochrome P450 family of enzymes. This leads to a cluster of dozens of common drugs interacting with one another to varying degrees, some of which are especially noteworthy: Oxcarbazepine and licarbazepine are potent inhibitors of CYP2C19 and thus have the potential to increase plasma concentration of drugs, which are metabolized through this pathway. Other antiepileptics, which are CYP2C19 substrates and thus may be metabolised at a reduced rate when combined with oxcarbazepine include diazepam, hexobarbital, mephenytoin, methylphenobarbital, nordazepam, phenobarbital, phenytoin, primidone. However, many classes of drugs are ligands to CYP2C19. In addition, oxcarbazepine and licarbazepine are CYP3A4 and CYP3A5 inducers and thus have the potential to decrease the plasma concentration of CYP3A4 and CYP3A5 substrates.
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Clomipramine may interact with a number of different medications, including the monoamine oxidase inhibitors which include isocarboxazid, moclobemide, phenelzine, selegiline and tranylcypromine, antiarrhythmic agents (due to the effects of TCAs like clomipramine on cardiac conduction. There is also a potential pharmacokinetic interaction with quinidine due to the fact that clomipramine is metabolised by CYP2D6 in vivo), diuretics (due to the potential for hypokalaemia (low blood potassium) to develop which increases the risk for QT interval prolongation and torsades de pointes), the selective serotonin reuptake inhibitors (SSRIs; due to both potential additive serotonergic effects leading to serotonin syndrome and the potential for a pharmacokinetic interaction with the SSRIs that inhibit CYP2D6 [e.g. fluoxetine and paroxetine]) and serotonergic agents such as triptans, other tricyclic antidepressants, tramadol, etc. (due to the potential for serotonin syndrome).
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Plasma half life is between 3 and 4 hours and oral/intramuscular analgesic potency ratio is approximately equal to 1:1.5. The most common conversion ratio, given on equianalgesia charts used in the United States, Canada, the UK, Republic of Ireland, the European Union, Russia and elsewhere as 130 mg IM equals 200 mg PO—both of which are equivalent to 10 mg of morphine sulphate IV and 60 mg of morphine sulphate PO. The salt:freebase ratio of the salts of both drugs in use are roughly equivalent, and do not generally make a clinical difference.The Merck Index, 13th Edition: Morphine Hydrochloride Codeine is metabolised by O- and N-demethylation in the liver to morphine and norcodeine. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid.
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Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases. Megavitamin therapy is typically used in alternative medicine by practitioners who call their approach orthomolecular medicine. Vitamins are useful in preventing and treating illnesses specifically associated with dietary vitamin shortfalls, but the conclusions of some medical research are that the claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. This seems to point to doses of any vitamin greatly in excess of nutritional requirements resulting either in toxicity (vitamins A and D) or in the excess simply being metabolised; thus the evidence in favour of vitamin supplementation supports only doses in the normal range.
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Levels of methanol, present as a congener in alcohol, have been correlated with severity of hangover and methanol metabolism to the highly toxic formate via formaldehyde coincides with the rate of appearance of hangover symptoms.Ylikahri RH, Huttunen M, Eriksson CJ, Nikkila EA. Metabolic studies on the pathogenesis of hangover. Eur J Clin Invest 1974;4:93–100 As both ethanol and methanol are metabolised by alcohol dehydrogenase – and ethanol is a much better substrate for this enzyme – drinking more of the former then effectively prevents (or delays) the metabolism of the latter. As pure ethanol consumption has also been found to increase endogenous levels of methanol, presumably for this reason, this suggests that if "hair of the dog" works in this way it effects a temporary hiatus rather than a cure.
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SN 35210 is an arylcyclohexylamine dissociative anesthetic drug. It was derived from ketamine with the intention of producing a shorter acting agent more suitable to be used as a stand-alone drug, whereas ketamine itself generally has to be used in combination with other drugs such as midazolam to minimise the occurrence of emergence reactions due to its hallucinogenic side effects. In common with other short-acting anaesthetic drugs such as remifentanil and remimazolam, SN 35210 has had the chemical structure modified to incorporate a methyl ester group which is rapidly metabolised to a carboxylic acid, producing an inactive compound and thus rapidly terminating the effects of the drug. It was selected for development from a series of structurally related alkyl esters due to having the shortest duration of action and the most similar pharmacological profile to ketamine itself.
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Decompression profiles based on the Thermodynamic model compared with the US Navy table for the same depth and bottom time The thermodynamic model was one of the first decompression models in which decompression is controlled by the volume of gas bubbles coming out of solution. In this model, pain only DCS is modelled by a single tissue which is diffusion-limited for gas uptake and bubble-formation during decompression causes "phase equilibration" of partial pressures between dissolved and free gases. The driving mechanism for gas elimination in this tissue is inherent unsaturation, also called partial pressure vacancy or the oxygen window, where oxygen metabolised is replaced by more soluble carbon dioxide. This model was used to explain the effectiveness of the Torres Straits Island pearl divers empirically developed decompression schedules, which used deeper decompression stops and less overall decompression time than the current naval decompression schedules.
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The water supplied to the laterals by the sinker root is continually lost to the soil; thus this plant facilitates the movement of ground water from the water table into surface soil, a process known as hydraulic redistribution. Cluster roots have been estimated as comprising about 30% of total root biomass in this species; the seasonal production of so much biomass, only for it to be lost at the end of the growing season, represents a substantial investment by the plant, but one that is critical in the competition for nutrients. During winter, asparagine is metabolised immediately, but other nutrients, especially phosphates and glutamine, are removed from the xylem sap and stored in mature stem, bark and leaf tissues for release back into the xylem just before shoot growth begins in mid summer. This is also the time when the oldest leaves senesce and die, returning nutrients to the plant at the time when they are needed most.
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Russell's earlier mutagenesis work on Drosophila using diethylnitrosoamine (DEN) triggered them to use DEN for the SLT. However, DEN needs to be enzymatically converted into an alkylating agent in order to be mutagenic and probably this enzymatic activation was not sufficient in mammals. This could be illustrated by the extremely low mutation rate in mice given by DEN (3 in 60,179 offspring). To overcome this problem, a new mutagen, N-ethyl N-nitrosourea (ENU), an alkylating agent, which does not need to be metabolised, was suggested to be used by Ekkehart Vegel to Russell et al. The ENU (250 mg/kg) induced mice underwent a period of sterility for 10 weeks. After recovery, 90 males were crossed to the T-stock females and 7584 pups were obtained. Their results showed that a dose of 250 mg/kg of ENU was capable of producing a mutation rate 5 times higher than that obtained with 600R (1R = 2.6 x10^-4 coulombs/kg) of acute X-irradiation. This rate was also 15 times higher to that obtained with procarbazine (600 mg/kg).
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