Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation.

摘要: Summary We retrospectively examined the association of polymorphisms in CYP3A, CYP2J2, CYP2C8, and ABCB1 genes with pharmacokinetic (PKs) pharmacodynamic (PDs) parameters tacrolimus 103 renal transplant recipients for a period 1 year. CYP3A5 expressers had lower predose concentrations (C0)/dose higher dose requirements than nonexpressers throughout study. Among CYP3A5*1 carriers, those also carrying CYP3A4*1B allele showed lowest C0/dose, as compared CYP3A4*1/CYP3A5*3 carriers (54.28 ± 26.45, 59.12 ± 24.00, 62.43 ± 41.12, 57.01 ± 17.34 vs. 112.37 ± 76.60, 123.21 ± 59.57, 163.34 ± 76.23, 183.07 ± 107.82 at week, month, 5 months, year after transplantation). In addition, CYP3A4*1B/CYP3A5*1 significantly dose-corrected exposure CYP3A4*1/CYP3A5*1 transplantation (57.01 ± 17.34 100.09 ± 24.78; P = 0.016). Only TGC (3435-2677-1236) haplotype consistent PDs (nephrotoxicity; OR = 4.73; CI: 1.3–16.7; P = 0.02). Our findings indicate that CYP3A4*1B-CYP3A5*1 may have more profound impact PKs allele. This study does not support critical role CYP450 or single nucleotide occurrence toxicity acute rejection treated tacrolimus.