Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole

Chiyo Imamura, Kenichi Furihata, Shinichiro Okamoto, Yusuke Tanigawara

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

This study evaluated the effects of cytochrome P450 (CYP) 2C19 polymorphisms on tacrolimus pharmacokinetics when coadministered with voriconazole. Eighteen healthy volunteers, including 6 individuals in each CYP2C19 genotype (extensive metabolizers [EMs], intermediate metabolizers [IMs], and poor metabolizers [PMs]), received a single oral dose of 3 mg tacrolimus alone or in combination with 200 mg voriconazole twice daily at steady state. When tacrolimus was coadministered with voriconazole, a significant increase in area under its concentration-time curve (AUC0-24) was observed for all genotypes. AUC0-12 of voriconazole in IMs and PMs were significantly higher than that in EMs (P 0-24 of tacrolimus in combination with voriconazole in IMs and PMs were also significantly higher than that in EMs (P

Original languageEnglish
Pages (from-to)408-413
Number of pages6
JournalJournal of Clinical Pharmacology
Volume56
Issue number4
DOIs
Publication statusPublished - 2016 Apr 1

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Keywords

  • CYP2C19 polymorphism
  • CYP3A
  • drug interaction
  • tacrolimus
  • voriconazole

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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