Some medications which have been thought to cause increased renal clearance include norepinephrine and other vasopressors. While medications may increase renal clearance, many patients with severe illness have higher clearance prior to the initiation of these medications. Augmented renal clearance also may occur in people who have some types of cancers, such as hematologic cancers. In these people, the efficacy of antibiotic treatment may be decreased if the increased clearance is not accounted for.
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Thus, total body clearance is equal to the sum clearance of the substance by each organ (e.g., renal clearance + hepatic clearance + lung clearance = total body clearance). For many drugs, however, clearance is solely a function of renal excretion. In these cases, clearance is almost synonymous with renal clearance or renal plasma clearance.
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Cefditoren is predominantly eliminated by the kidneys as unchanged drug and has a renal clearance of 4.1–5.6 L/h after multiple doses; its elimination half-life is 1.5 hours.
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In pharmacology, augmented renal clearance (ARC) is a phenomenon where certain critically ill patients may display increased clearance of a medication through the kidneys. In many cases, it is observed as a measured creatinine clearance above that which is expected given the patient's age, gender, and other factors. The phenomenon is most commonly observed in patients with neurologic damage, sepsis, major trauma, or burns. Augmented renal clearance can be caused by increased fluid administration, certain medications, and critical illnesses.
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Diagram showing the basic physiologic mechanisms of the kidney The kidney's ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion, whose sum is called renal clearance or renal excretion. That is: :Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion ratep 314, Guyton and Hall, Medical Physiology, 11th edition Although the strictest sense of the word excretion with respect to the urinary system is urination itself, renal clearance is also conventionally called excretion (for example, in the set term fractional excretion of sodium).
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The difference in a drug's concentration in arterial blood (before it has circulated around the body) and venous blood (after it has passed through the body's organs) represents the amount of the drug that the body has eliminated or cleared. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Clearance is therefore expressed as the plasma volume totally free of the drug per unit of time, and it is measured in units of volume per units of time. Clearance can be determined on an overall, organism level («systemic clearance») or at an organ level (hepatic clearance, renal clearance etc.).
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Various calculations and methods are used to try to measure kidney function. Renal clearance is the volume of plasma from which the substance is completely cleared from the blood per unit time. The filtration fraction is the amount of plasma that is actually filtered through the kidney. This can be defined using the equation.
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In young and healthy adults, the elimination half-life of doripenem considering the average plasma terminal is normally around 1 hour. The plasma clearance is about 15.9 L/hour and the average renal clearance is 10.3 L/hour. Research indicates doripenem is filtered by the glomerular capillary bed in Bowman’s capsule and the tubular secretions in the nephron.
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Urine specimens showed that no other microbiologically active metabolites were present except cephaloridine and that cephaloridine is excreted unchanged. Renal clearances were reported to be 146–280 ml/min, a plasma clearance of 167 ml/min/1,73m2 and a renal clearance of 125 ml/min/1,73m2. A serum half-life of 1,1-1,5 hour and a volume of distribution of 16 liters were reported.
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The use of LMWH needs to be monitored closely in patients at extremes of weight or in-patients with renal dysfunction. An anti-factor Xa activity may be useful for monitoring anticoagulation. Given its renal clearance, LMWH may not be feasible in patients that have end-stage renal disease. LMWH can also be used to maintain the patency of cannulae and shunts in dialysis patients.
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Forced alkaline diuresis has been used to increase the excretion of acidic drugs like salicylates and phenobarbitone, and is recommended for rhabdomyolysis. For forced acid diuresis, ascorbic acid (vitamin C) is sometimes used. Ammonium chloride has also been used for forced acid diuresis but it is a toxic compound. Usually however, this technique only produces a slight increase in the renal clearance of the drug.
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Reaction of acecainide Renal clearance of acecainide following short and long term administration ranges from 2.08±0.36 mL/min/kg to 3.28±0.52 mL/min/kg in healthy people. There is a linear relationship between acecainide clearance and creatinine clearance. However, the clearance of acecainide was reduced in a few patients with cardiomyopathyand and ventricular arrhythmias. Also is excretion of procainamide and NAPA is reduced in patients with CKD.
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The osmoregulatory system is interconnected with the circulatory system to permit effective regulation of salt and water balance. Circulatory fluids function in renal clearance, which is the blood volume that substances are removed from within the kidneys during a certain time period. In addition to filtration, the circulatory system also plays a role in reabsorption. Furthermore, the role of the renal portal system is to regulate renal hemodynamics during times of decreased arterial blood pressure.
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About 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (about 20% in urine and 25% in feces). A total of 96 ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (± SD) apparent total body clearance and renal clearance are 12 ± 2 L/h and 2.6 ± 0.5 L/h, respectively. The CSF penetration of moxifloxacin is 70% to 80% in patients with meningitis.
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Research shows that accumulation of acecainide during procainamide therapy can alter both procainamide elimination as well as its electrophysiologic actions. A few healthy people demonstrated that concomitantly administered trimethoprim decreased the renal clearance of procainamide and formed NAPA, resulting in increased plasma concentrations of both drugs and increases in QTc after procainamide. Trimethoprim, procainamide and acecainide are all excreted by active tubular secretion. Also amiodarone, cimetidine and trimethoprim increase the NAPA serum level.
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At its simplest, the kidney produces urine composed of solute and pure (solute-free) water. How rapidly the kidney clears the blood plasma of a substance (be it water or solute) is the renal clearance, which is related to the rate of urine production. The rate at which plasma is cleared of solute is the osmolal clearance; the rate at which plasma is cleared of solute-free water is the free water clearance.
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Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective effects. Unlike GIP, the action of GLP-1 is preserved in patients with type 2 diabetes and substantial pharmaceutical research has therefore been directed towards the development of GLP-1-based treatment. However, endogenous GLP-1 is rapidly degraded primarily by dipeptidyl peptidase-4 (DPP-4), but also neutral endopeptidase 24.11 (NEP 24.11) and renal clearance, resulting in a half-life of approximately 2 minutes.
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PAH is different from inulin in that the fraction of PAH that bypasses the glomerulus and enters the nephron's tubular cells (via the peritubular capillaries) is completely secreted. Renal clearance of PAH is thus useful in calculation of renal plasma flow (RPF), which empirically is (1-hematocrit) times renal blood flow. Of note, the clearance of PAH is reflective only of RPF to portions of the kidney that deal with urine formation, and, thus, underestimates the actual RPF by about 10%.Costanzo, Linda.
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Drug elimination is primarily facilitated via the liver and kidneys. In infants and young children, the larger relative size of their kidneys leads to increased renal clearance of medications that are eliminated through urine. In preterm neonates and infants, their kidneys are slower to mature and thus are unable to clear as much drug as fully developed kidneys. This can cause unwanted drug build-up, which is why it is important to consider lower doses and greater dosing intervals for this population.
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The conjugation of polyethylene glycol (PEG) chains to potential drug candidates extends the stability against proteases in body fluids and at the same time reduces renal clearance and immunogenicity. The first application described here, deals with the formation of protein-protein conjugates through bioorthogonal probes.Hudak, J. E., Barfield, R. M., de Hart, G. W., Grob, P., Nogales, E., Bertozzi, C. R. and Rabuka, D. (2012) Synthesis of Heterobifunctional Protein Fusions Using Copper-Free Click Chemistry and the Aldehyde Tag. Angew. Chem. Int.
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In patients who do not have their creatinine clearance or eGFR measured or calculated frequently, augmented renal clearance may be first seen by the failure of certain medications to produce the expected effect in a patient. As an example, an antibiotic that is being administered at recommended doses in accordance with antibiotic sensitivity testing may not be inducing clinical improvement in a person. This may also be recognized if calculated dosages based on pharmacokinetic monitoring are higher than expected for a patient.
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Augmented renal clearance may result in failure of treatment due to the increased elimination of drugs. This can be prevented by increasing the dosage of the medication, or by increasing the frequency the medication is administered to account for increased elimination. ARC influences the recommended dosages for antibiotics including aminoglycosides, beta-lactams, fluoroquinolones, and vancomycin in critical care. In any case, the occurrence of ARC is managed through pharmacokinetic monitoring and adjusting medication dosages, frequencies, or timing to ensure adequate response.
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The failure of clinical translation of nanoparticles-mediated PTT is mainly ascribed to body persistence concerns. Indeed, the optical response of anisotropic nanomaterials can be tuned in the NIR region by increasing their size to up to 150 nm. On the other hand, body excretion of non- biodegradable noble metals nanomaterials above 10 nm occurs through the hepatobiliary route in a slow and inefficient manner. A common approach to avoid metal persistence is to reduce the nanoparticles size below the threshold for renal clearance, i.e.
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The rate of metabolism of primidone into phenobarbital was inversely related to age; the highest rates were in the oldest patients (the maximum age being 55). People aged 70–81, relative to people aged 18–26, have decreased renal clearance of primidone, phenobarbital, and PEMA, in ascending order of significance, and that there was a greater proportion of PEMA in the urine. The clinical significance is unknown. The percentage of primidone converted to phenobarbital has been estimated to be 5% in dogs and 15% in humans.
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Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug, necessitating frequent dosing. Methods for mass production of penicillin were patented by Andrew Jackson Moyer in 1945.Andrew Jackson Moyer, Method for Production of Penicillin, United States Patent Office, US Patent 2,442,141, filed 11 May 1945, issued 25 March 1948.Andrew Jackson Moyer, Method for Production of Penicillin, United States Patent Office, US Patent 2,443,989, filed 11 May 1945, issued 22 June 1948.
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Although bone scintigraphy generally refers to gamma camera imaging of 99mTc radiopharmaceuticals, imaging with positron emission tomography (PET) scanners is also possible, using fluorine-18 sodium fluoride ([18F]NaF). For quantitative measurements, 99mTc-MDP has some advantages over [18F]NaF. MDP renal clearance is not affected by urine flow rate and simplified data analysis can be employed which assumes steady state conditions. It has negligible tracer uptake in red blood cells, therefore correction for plasma to whole blood ratios is not required unlike [18F]NaF.
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Renal excretion occurs by both glomerular filtration and tubular secretion as evidenced by the high rate of renal clearance (approximately 275 mL/min). Within 24 hours of drug administration, 26 to 32% of the administered dose is recovered in the urine as norfloxacin with an additional 5-8% being recovered in the urine as six active metabolites of lesser antimicrobial potency. Only a small percentage (less than 1%) of the dose is recovered thereafter. Fecal recovery accounts for another 30% of the administered dose.
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Military data suggest that the risk of exertional rhabdomyolysis can be lowered by engaging in prolonged lower-intensity exercise, as opposed to high-intensity exercise over a shorter time period. In all athletic programs, three features should be present: (1) emphasizing prolonged lower-intensity exercise, as opposed to repetitive max intensity exercises; (2) adequate rest periods and a high-carbohydrate diet, to replenish glycogen stores; and (3) proper hydration, to enhance renal clearance of myoglobin.Line, Robin L. Rust, George S. “Acute Exertional Rhabdomyolysis.” American Academy of Family Physicians.
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The plasma half-life for trospium chloride following oral administration is approximately 20 hours. After oral administration of an immediate-release formulation of 14C-trospium chloride, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8% of the dose) was recovered in urine; 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29 L/hour) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium.
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Ketoconazole: In-vitro replication studies have found a synergistic, dose- dependent antiviral activity against HSV-1 and HSV-2 when given with aciclovir. However, this effect has not been clinically established and more studies need to be done to evaluate the true potential of this synergy. Probenecid: Reports of increased half life of aciclovir, as well as decreased urinary excretion and renal clearance have been shown in studies where probenecid is given simultaneously with aciclovir. Interferon: Synergistic effects when administered with aciclovir and caution should be taken when administering aciclovir to patients receiving IV interferon.GlaxoSmithKline.
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The gamma subunit also seems to function as a protector of the alpha complex, preventing fast renal clearance or proteolytic degradation. It also boosts the specificity on the target and could be involved in the binding of the alpha unit. The whole complex is slightly acidic with a pH(I) of 5, but under a lower pH and/or high ionic strength the subunits dissociate. Just as the PLA2 enzyme the PLA2 toxin is Ca2+ dependent for hydrolysing fatty acyl ester bonds at the sn-2 position of glycerol-phospholipids.
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The molecular mass of crystallin and ubiquitin based Affilin proteins is only one eighth or one sixteenth of an IgG antibody, respectively. This leads to an improved tissue permeability, heat stability up to 90 °C (195 °F), and stability towards proteases as well as acids and bases. The latter enables Affilin proteins to pass through the intestine, but like most proteins they are not absorbed into the bloodstream. Renal clearance, another consequence of their small size, is the reason for their short plasma half-life, generally a disadvantage for potential drugs.
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When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15 h to 30 h), because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated. Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. A 10- to 20-fold increase in renal clearance occurs when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination.
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These recombinant hirudins lack a sulfate group at Tyr-63 and are therefore called desulfatohirudins. They have a 10-fold lower binding affinity to thrombin compared to native hirudin, but remain a highly specific inhibitor of thrombin and have an inhibition constant for thrombin in the picomolar range. Renal clearance and degradation account for the most part for the systemic clearance of desulfatohirudins and there is accumulation of the drug in patients with chronic kidney disease. These drugs should not be used in patients with impaired renal function, since there is no specific antidote available to reverse the effects.
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Staging of chronic kidney disease is based on categories of GFR as well as albuminuria and cause of kidney disease. Central to the physiologic maintenance of GFR is the differential basal tone of the afferent and efferent arterioles (see diagram). In other words, the filtration rate is dependent on the difference between the higher blood pressure created by vasoconstriction of the input or afferent arteriole versus the lower blood pressure created by lesser vasoconstriction of the output or efferent arteriole. GFR is equal to the renal clearance ratio when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys.
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It primarily cleaves peptides at the N-terminal side of aromatic amino acids or hydrophobic amino acids and is estimated to contribute by up to 50% of the GLP-1 degradation. However, the activity only becomes apparent once the degradation of DPP-4 has been prevented, as the majority of GLP-1 reaching the kidneys have already been processed by DPP-4. Similarly, renal clearance appear more significant for the elimination of already inactivated GLP-1. The resulting half-life of active GLP-1 is approximately 2 minutes, which is however sufficient to activate GLP-1 receptors.
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The primary sign of augmented renal clearance is an increase in the creatinine clearance well above that which would be considered normal. Commonly, ARC is defined as a creatinine clearance of greater than 130 mL/min, but the effects of increased clearance on therapy are not directly correlated to a specific number. For this reason, lower cutoffs such as 120 mL/min are used by some, as well as higher cutoffs in young people who typically have higher kidney function to begin with. Another cutoff used is 10% above the upper limit of normal for a certain population.
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009 The most common vehicle currently used for targeted drug delivery is the liposome. Liposomes are non-toxic, non-hemolytic, and non-immunogenic even upon repeated injections; they are biocompatible and biodegradable and can be designed to avoid clearance mechanisms (reticuloendothelial system (RES), renal clearance, chemical or enzymatic inactivation, etc.) Lipid-based, ligand-coated nanocarriers can store their payload in the hydrophobic shell or the hydrophilic interior depending on the nature of the drug/contrast agent being carried. The only problem to using liposomes in vivo is their immediate uptake and clearance by the RES system and their relatively low stability in vitro. To combat this, polyethylene glycol (PEG) can be added to the surface of the liposomes.
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