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

Chiyo K. Imamura, Kenichi Furihata, Shinichiro Okamoto, Yusuke Tanigawara

研究成果: Article査読

22 被引用数 (Scopus)

抄録

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 <.05 and P <.01, respectively). Consequently, AUC0-24 of tacrolimus in combination with voriconazole in IMs and PMs were also significantly higher than that in EMs (P <.05). These results demonstrate that CYP2C19 genotypes influenced the exposure of tacrolimus when coadministered with voriconazole, although tacrolimus is mainly metabolized by CYP3A.

本文言語English
ページ(範囲)408-413
ページ数6
ジャーナルJournal of Clinical Pharmacology
56
4
DOI
出版ステータスPublished - 2016 4 1

ASJC Scopus subject areas

  • 薬理学
  • 薬理学(医学)

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