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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  < .05 and  P  < .01, respectively). Consequently, AUC 0‐24  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.

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