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 <.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.
| Original language | English |
|---|---|
| Pages (from-to) | 408-413 |
| Number of pages | 6 |
| Journal | Journal of Clinical Pharmacology |
| Volume | 56 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2016 Apr 1 |
Keywords
- CYP2C19 polymorphism
- CYP3A
- drug interaction
- tacrolimus
- voriconazole
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)