Comparative Pharmacokinetics of Metabolism and Urinary Excretion of Isoxazolylpenicillins in Man

Abstract

Pharmacokinetic evaluations of cloxacillin and dicloxacillin in man were performed by detailed investigations of the urinary excretion profiles of the unchanged form and three metabolites (penicilloic acid, 5-hydroxymethyl derivative, and penicilloic acid of the 5-hydroxymethyl derivative). The last metabolite was newly found in human urine. The time course curves for excretion of unchanged form and the metabolites were measured by high performance liquid chromatography of urine excreted after oral administration of cloxacillin and dicloxacillin to human subjects. The values of cumulative excretion amount at infinite time (X∞u) and of mean residence time (MRT) for each species were estimated by moment analysis of excretion rate vs. time curves. The metabolic pathways of cloxacillin and dicloxacillin were assessed, and the transfer ratio at each elimination step and the MRT value intrinsic to each metabolite were evaluated from the results of moments. On the basis of these and the previous results for oxacillin and flucloxacillin, the pharmacokinetic features of four isoxazolylpenicillins are compared in terms of statistical moments. The extent and rate of total bioavailable activity due to the unchanged form and 5-hydroxymethyl metabolite are also discussed comnarativelv. © 1983, The Pharmaceutical Society of Japan. All rights reserved.