期刊
TRANSPLANT INTERNATIONAL
卷 25, 期 4, 页码 471-480出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1432-2277.2012.01446.x
关键词
ABCB1; CYP3A; polymorphisms; renal transplant; tacrolimus
资金
- Junta de Extremadura, Consejeria de Economia, Comercio e Innovacion, Merida (Spain) [GR10022]
- Fundesalud, Merida (Spain) [PRiS113]
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 (C0)/dose and higher dose requirements than nonexpressers throughout the study. Among CYP3A5*1 carriers, those also carrying the CYP3A4*1B allele showed the lowest C0/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: 1.316.7; 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.
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