Clearance glomerular filtration rate

Lenle, F, V, and Suit, P (1989). Assessment of renal function by serum creatinine and creatinine clearance Glomerular filtration rate estimated by four procedures. Our. Cfiem. 35, 2,326-2330. 

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

Creatinine clearance The rate at which creatinine is filtered across the glomerulus an estimate of glomerular filtration rate. 

Example. Kanamycin is a member of the aminoglycoside class of antibiotics, all of which are eliminated exclusively by glomerular filtration. Creatinine is a natural body substance that is cleared almost exclusively by glomerular filtration, and creatinine clearance rate is frequently used as a diagnostic tool to determine glomerular filtration rate. The relationship... 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Explain how plasma clearance of inulin is used to determine glomerular filtration rate... 

CKD may alter nonrenal clearance of drugs as the result of changes in cytochrome P450-mediated metabolism in the hver and other organs. The clinical reductions in nonrenal clearance in CKD are generally proportional to the reductions in glomerular filtration rate (Table 77-1). 

From a scientific point of view, glomerular filtration rate (inulin or creatinine clearance) is the best global estimate of renal function. Other parameters of interest include, but are not limited to ... 

After either oral or intravenous administration of ondansetron to laboratory animals the elimination of the drug is rapid. The short elimination half-lives t ji Table 7.7) reflect the high plasma clearance (CLp) in these species. Renal clearance (CLr) is below glomerular filtration rate, indicating that the major component of systemic clearance is metabolism. Ondansetron is rapidly absorbed after oral administration, peak concentrations in plasma being achieved within 40 min of dosing. However, the oral bioavailability is low. The similarity between concentrations of total drug-related material in plasma after oral and intravenous doses indicates that the low... 

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). 

The marker remains in the plasma without binding to proteins, and the filtrate is neither reabsorbed nor secreted by the renal tubule. Clearance rate of the marker from plasma equals the glomerular filtration rate (GFR). The polysaccharide, inulin, typifies this class of markers. 

Jenkins et al. developed a capillary electrophoresis system for the measurement of iohexol as a marker of the glomerular filtration rate (GFR) with a run time of 5.25 min and a coefficient of variation (CV) of 4.3% at 80 mg L" [121]. The GFR, calculated from the plasma clearance, had a reproducibility of 5.47 %. A similar approach (liquid chromatography-mass spectrometry with positive electrospray ionization after enrichment by solid phase extraction) was applied by Putschew et al. for the determination of iodinated contrast agents in treatment plant effluents and surface waters [118]. 

Renal function impairment No changes were observed in the pharmacokinetics of dipyridamole or its glucuronide metabolite with creatinine clearances ranging from approximately 15 mL/min to more than 100 mL/min if data were corrected for differences in age. Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/min). 

The systemic clearance of lepirudin is proportional to the glomerular filtration rate or creatinine clearance. Dose adjustment based on creatinine clearance is recommended (see Administration and Dosage). In patients with marked renal insufficiency (creatinine clearance less than 15 mL/min) and on hemodialysis, elimination half-lives are prolonged 2 days or less. 

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 - 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. 

So the total clearance of any drug is given by Vd (1) X Ks (h ) = (Vd /fei) 1/h, and is expressed, as is for example glomerular filtration rate, as units of volume per time period. We will use this concept of measuring clearance later in this section, and in clinical applications in Section IV. Tables of drug clearance are commonly set alongside those for apparent volume of distribution of common drugs in textbooks which list kinetic data. 

It is well known that both glomerular and tubular renal functions decline with age in at least one third of individuals. As a result there is greater variation in renal function in older subjects. Glomerular filtration rate can be predicted by creatinine clearance, which can be estimated based on measured serum creatinine (Sercr) concentration. One such formula is the Cochrane and Gault formula in which... 

Subsequent to the ingestion of iodine in various forms, I is absorbed by the small intestine and enters the blood. Two competing pathways are involved in the clearance of I from the blood renal filtration into urine and thyroidal uptake. The renal clearance rate for I (30-50 mL/minute) varies only with the glomerular filtration rate. However, the thyroidal 1 clearance rate is autoregulated to maintain an absolute thyroidal I uptake rate of approximately 100 jig I each day. To accomphsh this, the thyroidal I clearance rate may vary (3 to 100 mL/minute) depending on the concentration of I in the blood. 

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