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Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole
Author(s) -
Imamura Chiyo K.,
Furihata Kenichi,
Okamoto Shinichiro,
Tanigawara Yusuke
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.605
Subject(s) - voriconazole , tacrolimus , cyp2c19 , pharmacokinetics , cyp3a , pharmacology , medicine , cyp3a4 , drug interaction , area under the curve , cytochrome p450 , pharmacogenetics , genotype , chemistry , transplantation , metabolism , antifungal , biochemistry , dermatology , gene
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.