Pharmacokinetic and CYP3A5 pharmacogenetic differences between once- and twice-daily tacrolimus from the first dosing day to 1 year after renal transplantation.

Abstract

Aim & patients & methods: This study investigated 24-h pharmacokinetic and CYP3A5 pharmacogenetic differences between once-daily tacrolimus (Tac-q.d.) versus twice-daily tacrolimus (Tac-b.i.d.) pretransplantation and at 1 month and 1 year post-transplantaion. The dose-adjusted trough level (Cmin) and area under the blood concentration-time curve from 0 to 24 h (AUC₀₋₂₄) increased twofold within 1 year post-transplantation with both formulations and the two genotypes. Good correlations were observed between the AUC₀₋₂₄ and Cmin for both formulations. However, the dose-adjusted Cmin, but not dose-adjusted AUC₀₋₂₄, was approximately 30% lower for Tac-q.d. than for Tac-b.i.d. Although the dose-adjusted Cmin was lower for Tac-q.d. than for Tac-b.i.d. in both genotypes, the dose-adjusted AUC₀₋₂₄ was approximately 25% lower for Tac-q.d. than for Tac-b.i.d. in CYP3A5 expressers, but not in nonexpressers during the study period. These results suggested that the approximately 30% lower Cmin for Tac-q.d. than for Tac-b.i.d. may have achieved the same AUC₀₋₂₄ with both formulations and may be associated with CYP3A5 pharmacogenomic differences, especially in CYP3A5 expressers, between Tac-b.i.d. and Tac-q.d.