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

Author:

Satoh Shigeru1,Niioka Takenori2,Kagaya Hideaki2,Numakura Kazuyuki3,Inoue Takamitsu3,Saito Mitsuru3,Komine Naoki3,Narita Shintaro3,Tsuchiya Norihiko3,Habuchi Tomonori3,Miura Masatomo2

Affiliation:

1. Center for Kidney Disease & Transplantation, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan

2. Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan

3. Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan

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. Results: 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. Conclusion: 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. Original submitted 3 May 2013; Revision submitted 11 June 2014

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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