伏立康唑
CYP2C19型
他克莫司
药代动力学
CYP3A型
药理学
CYP3A4型
医学
药物遗传学
药物相互作用
CYP2D6型
细胞色素P450
基因型
内科学
化学
移植
新陈代谢
抗真菌
生物化学
皮肤病科
基因
作者
Chiyo K. Imamura,Kenichi Furihata,Shinichiro Okamoto,Yusuke Tanigawara
摘要
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 < .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.
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