Impact of CYP3A5 Genetic Polymorphism on Intrapatient Variability of Tacrolimus Exposure in Chinese Kidney Transplant Recipients

Background. Although high tacrolimus (FK) intrapatient variability (IPV) was shown to be associated with poor graft outcome in kidney transplant recipients (KTRs), it is uncertain whether there is any association between the CYP3A5 genotype and IPV of FK concentrations. Instead of trough level, we use calculated abbreviated AUC(0-12) to investigate the impact of CYP3A5 genetic polymorphism on IPV of FK pharmacokinetics.

Methods. We conducted a retrospective, single-center study of 86 adult Chinese KTRs with known CYP3A5 genotype. Coefficient of variation (CV) was used for the quantification of FK IPV. CV of dose-normalized FK AUC(0-12) was calculated and was compared between the CYP3A5 expresser group and nonexpresser group.

Results. Forty-one patients (47.7%) were classified as CYP3A5 expressers while 45 were nonexpressers. No significant differences in the baseline characteristics were found between expressers and nonexpressers. CYP3A5 expressers required 1.8 times higher FK dose compared with the nonexpressers. There was no significant difference in the FK CV between CYP3A5 expressers (18.2 +/- 7.5%) and nonexpressers (16.7 +/- 5.7%) (P = .31).

Conclusion. The IPV of FK exposure was not associated with CYP3A5 genotype in stable KTRs. Further studies should focus on other factors such as medication nonadherence, which may explain FK IPV.