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

Chiyo Imamura; Kenichi Furihata; Shinichiro Okamoto; Yusuke Tanigawara

doi:10.1002/jcph.605

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 journal › Article

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 (AUC_0-24) was observed for all genotypes. AUC_0-12 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 language	English
Pages (from-to)	408-413
Number of pages	6
Journal	Journal of Clinical Pharmacology
Volume	56
Issue number	4
DOIs	https://doi.org/10.1002/jcph.605
Publication status	Published - 2016 Apr 1

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Keywords

CYP2C19 polymorphism
CYP3A
drug interaction
tacrolimus
voriconazole

ASJC Scopus subject areas

Pharmacology (medical)
Pharmacology

Cite this

Imamura, C., Furihata, K., Okamoto, S., & Tanigawara, Y. (2016). Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole. Journal of Clinical Pharmacology, 56(4), 408-413. https://doi.org/10.1002/jcph.605

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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 ",

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10.1002/jcph.605