Effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers

Mutsuko Honda, Takashi Nozawa, Norio Igarashi, Hiroshi Inoue, Rie Arakawa, Yumi Ogura, Hiromi Okabe, Masato Taguchi, Yukiya Hashimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

This study was performed to investigate the effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers. Five or 10 mg of carvedilol was orally administered to 23 subjects (22-44 years old), and blood samples were taken at 2 and 6 h after dosing. We determined the polymorphic alleles of CYP2D6 in each subject. The whole blood concentration of R- and S-carvedilol was measured by an HPLC method. The pharmacokinetic parameters in individual subjects were estimated by the Bayesian method using the nonlinear mixed effects model (NONMEM) program. The mean values of oral clearance for R- and Scarvedilol were estimated to be 1.01 and 2.15 l/h/kg, respectively. The oral clearance was highly correlated with the apparent volume of distribution among the subjects, suggesting that the interindividual difference in bioavailability was largely responsible for the pharmacokinetic variability of carvedilol. The oral clearance and also volume of distribution of both enantiomers were significantly lower in the subjects with the CYP2D6*10 allele than with the CYP2D6*1/*1 or *1/*2 genotype. These results suggested that the systemic and/or pre-systemic metabolism of R- and S-carvedilol in the liver is significantly decreased in Japanese with the CYP2D6*10 allele.

Original languageEnglish
Pages (from-to)1476-1479
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume28
Issue number8
DOIs
StatePublished - 2005/08

Keywords

  • Bayesian analysis
  • Carvedilol
  • Cyp2d6*10
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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