Population pharmacokinetics of higher-dose mizoribine in healthy male volunteers

Mutsuko Honda, Hiromichi Itoh, Tadakiyo Suzuki, Yukiya Hashimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The population pharmacokinetic parameters of mizoribine in healthy subjects were estimated using a nonlinear mixed effects model (NONMEM) program. Pharmacokinetic data for population analysis were obtained in the previous study, in which 24 healthy Caucasian male subjects participated in a single-dose (3, 6, 9, 12 mg/kg) study, and 12 subjects participated in a multiple-dose (6, 12 mg/kg/d) study. The mean value of the absorption lag time, absorption rate constant (KA), and apparent distribution volume (V/F) was estimated to be 0.349 h, 0.869 h-1, and 0.834 l/kg, respectively. Oral clearance (CL/F) was modeled with creatinine clearance (CLcr), and the mean value was estimated to be 1.93·CLcr l/h. In addition, pharmacokinetic parameters in individual 36 subjects were obtained from population estimates according to Bayes' theorem. Pharmacokinetic parameters (KA, V/F, and CL/F) in the single-dose study were almost constant at a dose range of 3-12 mg/kg, and were similar to those in the multiple-dose study. These findings indicated that the pharmacokinetics of mizoribine is well described by a simple one-compartment model with first-order absorption.

Original languageEnglish
Pages (from-to)2460-2464
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume29
Issue number12
DOIs
StatePublished - 2006/12

Keywords

  • Bayesian analysis
  • Mizoribine
  • Nonlinear mixed effect model
  • Population pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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