Biliary and renal excretions of cefpiramide in eisai hyperbilirubinemic rats

I. Muraoka, T. Hasegawa, M. Nadai, L. Wang, S. Haghgoo, O. Tagaya, T. Nabeshima

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Abstract

Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the β-lactam antibiotic cefpiramide (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 healthy 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 SDRs, significant decreases (by approximately 30%) in the systemic clearance 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 that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion.

Original languageEnglish
Pages (from-to)70-74
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume39
Issue number1
DOIs
Publication statusPublished - 1995

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Muraoka, I., Hasegawa, T., Nadai, M., Wang, L., Haghgoo, S., Tagaya, O., & Nabeshima, T. (1995). Biliary and renal excretions of cefpiramide in eisai hyperbilirubinemic rats. Antimicrobial agents and chemotherapy, 39(1), 70-74. https://doi.org/10.1128/AAC.39.1.70