BILIARY AND RENAL EXCRETIONS OF CEFPIRAMIDE IN EISAI HYPERBILIRUBINEMIC RATS

Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbili rubinemia were recently derived from Sprague-Dawley rats (SDRs). The p harmacokinetic characteristics of the beta-lactam antibiotic cefpirami de (CPM), which is mainly excreted into bile, were investigated in 10- and 20-week-old EHBRs and were compared with those in 20-week-old hea lthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SD Rs, significant decreases (by approximately 30%) in the systemic clear ance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of tha t in age-matched healthy SDRs, while total urinary recovery of unchang ed CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of C PM were observed between the two groups of EHBRs. There were no signif icant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubine mia induces an increase in the urinary excretion ability of CPM in ret urn for a reduction in the biliary excretion.