Kinetics of Renal Disposition and Action of Bioactive Peptides

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The purpose of the present study is to investigate the contribution of renal clearance on the whole body clearance quantitatively and to clarffy the kinetics of pharmacologic and toxic actions of peptide.We have investigated the renal excretion of vancomycin, a glycopeptide antibiotics. The population pharmacokinetic profile of vancomycin in Japanese patients was analyzed by using the NONMEN program. In adults, vancomycin clearance was linearly correlated with creatinine clearance(CLcr), when CLcr was less than 85 ml/min. In pediatric patients, vancouiycin clearance increased with age up to 1. year of age, and decreased with age over 1 year old. Based on these results, a nomogram that gives the relationship of the optimum dosing interval and the CLcr needed to achieve the steady state peak and trough concentrations of 50 ug/ml and 7.5 ug/ml, respectively, was proposed. Nonparametric binary regression analysis of the relationship between trough concentration and the rate of incidence of the abnormality in the kidney showed that the rate increased with the coadministration of aminoglycosid It is possible to reduce the rate to less than 15 % as long as the trough concentration is kept below 10 ug/mi.The pharmacokinetics of cyclosporin A, a peptidic immunodipressant, was also investigated in rats. It was shown that cyclosporin clearance was reduced by the coadministration of nicardipine, but not affected by nitroglycerin.