Excretion renal clearance

Excretion - Absorbed oseltamivir is primarily (more than 90%) eliminated by conversion to oseltamivir carboxylate. Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration. Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects. Oseltamivir carboxylate is eliminated entirely (more than 99%) by renal excretion. Renal clearance (18.8 L/h) exceeds glomerular filtration rate (7.5 L/h) indicating that tubular secretion occurs, in addition to glomerular filtration. Less than 20% of an oral dose is eliminated in feces. 

Pharmacokinetics Lepirudin is eliminated primarily by renal excretion (renal clearance 65 to 115ml/min). Dose adjustment based on creatinine clearance is recommended. The total clearance of lepirudin is 195ml/min, its elimination half-life is 1.3 hours, and its volume of distribution is 12.2 to 18.0 hters.The systemic clearance of lepirudin in women is about 25% lower than in men. In elderly patients the systemic clearance of lepirudin is 20% lower than in younger patients. Distribution is limited to extracellular space. As the intravenous dose is increased over the range of 0.1 to 0.4mg/kg, the maximum plasma concentration and the area-under-the-curve increase proportionally. 

The rate of urine amylase excretion is a sensitive reflection of the amylase released into the blood. The urine amylase remains abnormal 1-2 weeks after the serum returns to normal because the renal clearance of amylase rises 3-fold in acute pancreatitis and takes 1-2 weeks to return to normal. In pancreatitis, a number of investigators have reported a higher percentage of urinary amylase elevations, as contrasted with serum amylase elevations, particularly when the urinary amylase output over an interval is measured. Random urine collections for one, two and 24 hours are 792-4264 (2926 1074 S.D.) units per 24 hours. However, the wide range of normals make interpretation of results difficult. Of 107 patients with elevated serum or urine amylases, 16 were found to have a normal pancreas at operation (78). 

The study of the mechanism of urinary excretion of amylase and the amylase clearance has been the subject of many studies in recent years. Levitt et. al (79) studied the renal clearance of amylase in renal insufficiency, acute pancreatitis and macro-amylasemia. In acute pancreatitis, the kidney cleared amylase at a markedly increased rate. The ratio of the amylase clearance rate to the creatinine clearance rate (Cgm/Ccr) averaged 3 times normal early in the course of acute pancreatitis, and this elevation could persist after the serum amylase returned to normal. Comparison of an lase clearance to creatinine clearance was to minimize irrelevant changes due to variation in renal function. The increased clearance of amylase makes the urinary amylase a more sensitive indicator of pancreatitis. 

Despite their potential health-promoting effects as dietary antioxidants, the fate of betalains in humans has been poorly studied. Betalain bioavailability was first demonstrated in humans by the appearance of betacyanins in urines after ingestion of beetroot extract" and red beet juice," indicating that these compounds are indeed absorbed. Although intact betacyanins (betanin and isobetaiun) appeared rapidly in human urine with a maximum excretion rate observed within 2.5 to 8 hr," betacy-anin recoveries in human urine were usually low (< 1% of the dose) over 24 hr postdose, suggesting that either the bioavailabifity of betacyaiuns from red beetroot is low or that renal clearance is a minor excretion route for these compounds. 

Example. In the example plotted in Fig. 6, the amount of drug excreted over the 0- to 0.5-hour interval was 37.5 mg. If the plasma concentration at 0.25 hour (the middle of the interval) was lOpg/mL, what was the renal clearance rate From Eq. (18),... 

Aptamers appear to display low immunogenicity but, when administered systemically, they are quickly excreted via size-mediated renal clearance. In order to prevent renal removal, such aptamers are usually conjugated to PEG. PEG may also help further protect the aptamers from degradation by serum nucleases native aptamers are prone to nuclease attack, but their half-lives can most effectively be extended via chemical modification, as discussed earlier in the context of antisense agents. 

Hirom [71,72] demonstrated more than three decades ago that the route of excretion of xenobiotics is dependent upon MW by testing up to 75 compounds in rat, guinea-pigs, and rabbits. Lower MW compounds (< 350) were mainly eliminated in the urine (>90%). As MW increased from 350 to 450, a sharp increase in the fraction of compound eliminated in the bile occurred, and for MW > 450, compounds were eliminated 50-100% in the bile in all three species. Smith [73] correlated the log of free metabolic and renal clearance (ml/min/kg) with log D, and found a similar relationship. Metabolic clearance increases with increasing log D, while renal clearance decreases with increasing log D. 

The importance of insulin as a mediator of the hypercalciuric effect of arginine infusion was also evident from studies conducted in chronically diabetic rats, where diabetes was induced by strepto-zotocin (23). Animals were injected with streptozotocin prior to arginine infusion 100 mg/kg i.p. was given on the seventh day before, followed by 25 mg/kg six days before the arginine infusion and renal clearance studies. In contrast to non-diabetic controls, diabetic animals did not increase their urinary calcium excreted (per ml glomerular filtrate) in response to the arginine infusion, nor did the arginine stimulate insulin secretion. 

Clearance refers to the elimination of drug from the body. It is defined as the volume of blood which is completely cleared of drug per unit time. The drug can be eliminated via excretion through kidneys, and/or metabolism in liver, or through other routes such as saliva, milk, sweat, etc. The clearance associated with the kidney is called the renal clearance (C1r), and the clearance associated with other routes including metabolism is known as non-renal... 

Renal clearance of cotinine is much less than the glomerular filtration rate (Benowitz et al. 2008b). Since cotinine is not appreciably protein bound, this indicates extensive tnbnlar reabsorption. Renal clearance of cotinine can be enhanced by np to 50% with extreme urinary acidification. Cotinine excretion is less influenced by urinary pH than nicotine becanse it is less basic and, therefore, is primarily in the unionized form within the physiological pH range. As is the case for nicotine, the rate of excretion of cotinine is influenced by urinary flow rate. Renal excretion of cotinine is a minor route of elimination, averaging about 12% of total clearance. In contrast, 100% of nicotine Ai -oxide and 63% of 3 -hydroxycotinine are excreted unchanged in the urine (Benowitz and Jacob 2001 Park et al. 1993). 

Hepatic metabolism and excretion in the bile play major roles in the elimination of both vinblastine and vincristine in humans (52) small amounts of vincristine and vinblastine, of the order of 10% of the administered dose, are excreted unchanged in urine. Renal clearance of vinblastine has been reported to be less than 10% of total serum clearance 53). Vinblastine has been reported to inhibit a polymorphic cytochrome P-450 system in human hepatic microsomes, but the concentrations required were much higher than those observed in clinical settings (54). 

In calves and cows, SDM was excreted by glomerular filtration minus tubular reabsorption its renal clearance was urine flow correlated, and amounts to half of the creatinine clearance. The SCH2OH hydroxy metabolite was excreted by glomerular filtration and partly by tubular secretion, whereas both Na-SDM and SOH were excreted predominantly by tubular secretion (15 . The main metabolite in urine SCH2OH was 23 to 55 % of the administered dose (Table III). The urine concentration—time curves for SDM and its metabolites are illustrated in Figure 7 for a high SDM dosage. 

When hydroxylation is absent or negligible, both the position of the acetylation-deacetylation equilibrium and the renal excretion rate determine the elimination half-life. This can be exemplified by comparing the SDM disposition in pigs and man. The renal clearance values of N -SDM in both species are the same ( approximately 10 ml/min/kg), but in man the equilibrium favours the acetylated... 

The primary endpoint of the toxicokinetic studies is the concentration-time prohle of the substance in plasma/blood and other biological fluids as well as in tissues. The excretion rate over time and the amount of metabolites in urine and bile are further possible primary endpoints of kinetic studies, sometimes providing information on the mass balance of the compound. From the primary data, clearance and half-life can be derived by several methods. From the excretion rate over time and from cumulative urinary excretion data and plasma/blood concentration measured during the sampling period, renal clearance can be calculated. The same is the case for the bUiary excretion. 

Walton et al. (2004) determined the extent of interspecies differences in the internal dose of compounds, which are eliminated primarily by renal excretion in humans. Renal excretion was also the main route of elimination in the test species for most of the compounds. Interspecies differences were apparent for both the mechanism of renal excretion (glomemlar filtration, tubular secretion, and/or reabsorption), and the extent of plasma protein binding. Both of these may affect renal clearance and therefore the magnitude of species differences in the internal dose. For compounds which were eliminated unchanged by both humans and the test species, the average difference in the internal dose between humans and animals were 1.6 for dogs, 3.3 for rabbits, 5.2 for rats, and 13 for mice. This suggests that for renal excretion the differences between humans and the rat, and especially the mouse, may exceed the fourfold default factor for toxicokinetics. 

Clearance. Renal clearance is used as a quantitative measure of renal function. It is defined as the plasma volume cleared of a given substance per unit of time. Inulin, a fructose polysaccharide with a mass of ca. 6 kDa (see p. 40) that is neither actively excreted nor resorbed but is freely filtered, has a clearance of 120mb min in healthy individuals. 

Excretion - After IV administration of 1 mg to healthy males, plasma concentrations declined biexponentially with a redistribution and a terminal elimination half-life of 41 34 minutes and 10.8 5.2 hours, respectively. The systemic clearance of nalmefene is 0.8 L/h/kg and the renal clearance is 0.08 L/h/kg. 

Excretion - The plasma half-life for trospium following oral administration is approximately 20 hours. After administration of oral trospium, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8%) was recovered in urine 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29.07 L/h) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that also are renally eliminated. 

Excretion - The terminal elimination half-life is between 5 and 6 days following inhalation. After dry powder inhalation, urinary excretion is 14% of the dose, the remainder being mainly nonabsorbed drug in the gut, which is eliminated via the feces. The renal clearance of tiotropium exceeds the Ccr, indicating active secretion into the urine. After chronic, once-daily inhalation by COPD patients, pharmacokinetic steady state was reached after 2 to 3 weeks with no accumulation thereafter. 

Penicillin or cephalosporin therapy The PSP excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about the normal rate when dosage of probenecid is adequate. 

Metabolism/Excretion- Memantine undergoes little metabolism, with the majority (57% to 82%) of an administered dose excreted unchanged in urine. Memantine has a terminal elimination half-life of about 60 to 80 hours. Renal clearance involves active tubular secretion. 

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug, with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to Ccr. 

Excretion - Absorbed SP and 5-ASA and their metabolites are primarily eliminated in the urine either as free metabolites or as glucuronide conjugates. The majority of 5-ASA stays within the colonic lumen and is excreted as 5-ASA and acetyl-5-ASA with the feces. The calculated clearance of sulfasalazine following IV administration was 1 L/h. Renal clearance was estimated to account for 37% of total clearance. 

Excretion - Nonrenal clearance accounts for approximately 65% of the total clearance of linezolid. The renal clearance of linezolid is low and suggests net tubular reabsorption. 

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