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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)561-565
Number of pages5
JournalDrug Metabolism and Disposition
Volume22
Issue number4
Publication statusPublished - 01-01-1994

Fingerprint

Protein Binding
Pharmacokinetics
Hyperbilirubinemia
Sprague Dawley Rats
Kidney
enprofylline
Inulin
Glomerular Filtration Rate
Binding Sites
Urine
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

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title = "Alterations in the pharmacokinetics and protein binding of enprofylline in Eisai hyperbilirubinemic rats",
abstract = "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.",
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Alterations in the pharmacokinetics and protein binding of enprofylline in Eisai hyperbilirubinemic rats. / Nadai, M.; Hasegawa, T.; Wang, L.; Tagaya, O.; Nabeshima, Toshitaka.

In: Drug Metabolism and Disposition, Vol. 22, No. 4, 01.01.1994, p. 561-565.

Research output: Contribution to journalArticle

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T1 - Alterations in the pharmacokinetics and protein binding of enprofylline in Eisai hyperbilirubinemic rats

AU - Nadai, M.

AU - Hasegawa, T.

AU - Wang, L.

AU - Tagaya, O.

AU - Nabeshima, Toshitaka

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