Renal clearance calculation

The area under the PCP concentration-time curve (AUC) from the time of antibody administration to the last measured concentration (Cn) was determined by the trapezoidal rule. The remaining area from Cn to time infinity was calculated by dividing Cn by the terminal elimination rate constant. By using dose, AUC, and the terminal elimination rate constant, we were able to calculate the terminal elimination half-life, systemic clearance, and the volume of distribution. Renal clearance was determined from the total amount of PCP appearing in the urine, divided by AUC. Unbound clearances were calculated based on unbound concentrations of PCP. The control values are from studies performed in our laboratory on dogs administered similar radioactive doses (i.e., 2.4 to 6.5 pg of PCP) (Woodworth et al., in press). Only one of the dogs (dog C) was used in both studies. 

When we calculated systemic and renal clearance based on the area under the unbound PCP concentration-time curve, we found essentially no change in these parameters compared to the control studies without antibody (Woodworth et al., in press) (figure 6). 

Calculate measured creatinine clearance Calculate fractional excretion of sodium Plans for renal replacement... 

The term clearance is used here in the sense of total body clearance and is analogous to the term renal clearance. The body as a whole is regarded as acting as a xenobiotic-eliminating system, where the rate of elimination divided by the average plasma concentration of the compound is the total body clearance. Here clearance is calculated (25) by dividing the administered dose of the substance by the area under the plasma concentrationtime curve produced by that dose. This pharmacokinetic parameter, as well as others presented in this publication, was calculated by the use of the MLAB on-line computer system established at the National Institutes of Health by Knott and Reece (26). Similar to t the total clearance is a composite of the individual clearances of the material by the various tissues of the body. 

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. 

In addition to the pharmacokinetics of the drug, the first study in man can provide important information about its metabolites. If assay methodology has been developed, metabolites in plasma can be detected and the AUCs and half-lives determined. Further information can be obtained from assaying urine for drug and, if possible, metabolites. Renal clearance can be calculated over time intervals and the ratio of... 

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. 

The final clearance value that is frequently calculated is that of renal clearance, or that portion of clearance that is due to renal elimination. Renal clearance is calculated as ... 

Drugs cleared by the renal route often require adjustment of clearance in proportion to renal function. This can be conveniently estimated from the creatinine clearance, calculated from a single serum creatinine measurement and the predicted creatinine production rate. 

The decrease of renal function with age is independent of the decrease in creatinine production. Because of the difficulty of obtaining complete urine collections, creatinine clearance calculated in this way is at least as reliable as estimates based on urine collections. Fat-free mass (equation [14]) should be used for obese patients, and correction should be made for muscle wasting in severely ill patients. 

GFR and RPF can be measured without collection of urine by measuring the disappearance of the appropriate tracers from the blood over time (plasma clearance). In this technique, precise amounts of tracers are injected intravenously as a bolus and subsequent serial samples at precise intervals are collected. The disappearance of the tracer from the blood used to calculate the renal clearance (Bailey et al. 1970 Ronnhedh et al. 1996). 

For urine data, the individual and mean fractional and cumulative urinary excretion of XYZ1234 were calculated the cumulative excretion profiles were represented graphically fractional and total urinary excretion (Ae -tp Ae(0-48h))> urinary recovery (% of administered dose), and renal as well as non-renal clearance (CLR, CLNR) were determined. 

This dilemma is best avoided by calculating dialysis clearance using an equation that is analogous to the equation used to determine renal clearance ... 

Hepatic clearance (CLh) may be defined as the volume of blood perfusing the liver that is cleared of drug per unit time. Usually, hepatic clearance is equated with nonrenal clearance and is calculated as total body clearance (CLe) minus renal clearance (CLr) ... 

It can be seen from Equation 7.11 that oral doses of nonrestrictively metabolized drugs should not need to be adjusted in response to changes in hepatic blood flow. Equation 7.11 also forms the basis for using AUCoral measurements to calculate so-called oral clearance" as an estimate of fuCLint. However, if renal excretion contributes to drug elimination, it will reduce AUCorai and lead to over estimation of fuCLinf unless the contribution of renal clearance is accounted for (2). 

The adverse effects of mycophenolate mofetil in children have been reviewed retrospectively in 24 renal transplant patients (mean age 14 years) switched from azathioprine to mycophenolate mofetil a mean of 4.8 years after transplantation (42). The mean dose of mycophenolate mofetil was 560 mg/m. After a mean of 9.6 months, 13 had to discontinue treatment because of adverse effects, namely severe and partially reversible anemia (10 patients, of whom three required transfusions), neutropenia n — 1), and diarrhea n — 2). The anemia was normocytic and normochromic in nine patients, and such a high incidence of severe anemia was unexpected from the available adult data. Although patients who discontinued treatment had a lower pretreatment-calculated creatinine clearance, this was not significant and probably not the major cause of anemia. The author speculated that the anemia resulted from a disproportionately high unbound plasma concentration of mycophenolate mofetil, due to reduced protein binding and impaired renal clearance. 

Jacobson L. A method for the calculation of renal clearance based upon a single plasma sample. Clin Physiol 1983 3 297-305. 

Clearances for individual organs can be computed if the excretion the organ produces can be obtained. For example, renal clearance can be calculated if urine is collected during a pharmacokinetic experiment. The patient empties his or her bladder immediately before the dose is given. Subsequent urine production is collected until the last serum concentration (Ciasd is obtained. Renal clearance (CIr) is computed by dividing the amount of drug excreted in the urine by AUCo-/,iast-Bihary and other clearance values are computed in a similar fashion. 

Normal CCr may be considered as lOOml/minute once the CCr and LBM have been calculated the loading dose (initial dose) required to reach a certain serum concentration and the maintenance dose to maintain the specified concentration can be calculated. The loading dose (LD) is based solely on the LBM of the patient. The maintenance dose (MD) is based on LBM and the renal clearance rate of the drug. 

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