We retrospectively examined the association of polymorphisms in the CYP3A, CYP2J2, CYP2C8, and ABCB1 genes with pharmacokinetic (PKs) and pharmacodynamic (PDs) parameters of tacrolimus in 103 renal transplant recipients for a period of 1 year. CYP3A5 expressers had lower predose concentrations (C(0) )/dose and higher dose requirements than nonexpressers throughout the study. Among CYP3A5*1 carriers, those also carrying the CYP3A4*1B allele showed the lowest C(0) /dose, as compared with CYP3A4*1/CYP3A5*3 carriers (54.28±26.45, 59.12±24.00, 62.43±41.12, and 57.01±17.34 vs. 112.37± 76.60, 123.21±59.57, 163.34±76.23, and 183.07±107.82 at 1 week, 1 month, 5 months, and 1 year after transplantation). In addition, CYP3A4*1B/CYP3A5*1 carriers showed significantly lower dose-corrected exposure than CYP3A4*1/CYP3A5*1 carriers 1 year after transplantation (57.01±17.34 vs. 100.09±24.78; P=0.016). Only the ABCB1 TGC (3435-2677-1236) haplotype showed a consistent association with PDs (nephrotoxicity; OR=4.73; CI: 1.3-16.7; P=0.02). Our findings indicate that the CYP3A4*1B-CYP3A5*1 haplotype may have a more profound impact in tacrolimus PKs than the CYP3A5*1 allele. This study does not support a critical role of the CYP450 or ABCB1 single nucleotide polymorphisms in the occurrence of toxicity or acute rejection in renal transplant recipients treated with tacrolimus.
© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.