Alterations in the pharmacokinetics and protein binding of enprofylline in Eisai hyperbilirubinemic rats

M. Nadai, T. Hasegawa, L. Wang, O. Tagaya, T. Nabeshima

研究成果: Article

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Mutant rats possessing conjugated hyperbilirubinemia have recently been established from Sprague-Dawley rats (SDRs) and are called Eisai hyperbilirubinemic rats (EHBRs). The effects of hyperbilirubinemia on the disposition, renal handling, and protein binding behavior of enprofylline, which is mainly excreted into the urine by an active tubular secretion mechanism, were investigated in 9- and 19-week-old EHBRs and compared with their age-matched normal SDRs. Enprofylline was administered intravenously at a dose of 2.5 mg/kg, which exhibits linear kinetics. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model- independent methods. Both systemic clearance and volume of distribution at steady state of enprofylline significantly increased in 19-week-old EHBRs. However, there were no differences in the glomerular filtration rate estimated as inulin clearance and fraction of urinary excretion as unchanged drug between EHBRs and normal SDRs. Significant decreases in both the binding capacity and number of binding sites were observed in 19-week-old EHBRs, but no such changes were observed between 9-week-old EHBRs and SDRs. Hyperbilirubinemia in EHBRs had no effect on the pharmacokinetics and renal handling of unbound enprofylline. These results indicate that the pharmacokinetics of enprofylline, but not renal handling, glomerular filtration, or tubular secretion are modified in EHBRs by changes in protein binding behavior.

元の言語English
ページ(範囲)561-565
ページ数5
ジャーナルDrug Metabolism and Disposition
22
発行部数4
出版物ステータスPublished - 01-01-1994
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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    Nadai, M., Hasegawa, T., Wang, L., Tagaya, O., & Nabeshima, T. (1994). Alterations in the pharmacokinetics and protein binding of enprofylline in Eisai hyperbilirubinemic rats. Drug Metabolism and Disposition, 22(4), 561-565.