Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients

Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05–3.70 (ng·mL–1)/(mg·kg–1)) as compared with the expressors (1.15, 95%: 0.95–1.80 (ng·mL–1)/(mg·kg–1)) of CYP3A5 (Mann–Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA le...