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首页> 外文期刊>CPT: Pharmacometrics & Systems Pharmacology >Effect of CYP3A4*22, CYP3A5*3, and CYP3A Combined Genotypes on Cyclosporine, Everolimus, and Tacrolimus Pharmacokinetics in Renal Transplantation
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Effect of CYP3A4*22, CYP3A5*3, and CYP3A Combined Genotypes on Cyclosporine, Everolimus, and Tacrolimus Pharmacokinetics in Renal Transplantation

机译：CYP3A4 * 22，CYP3A5 * 3和CYP3A联合基因型对肾移植中环孢霉素，依维莫司和他克莫司药代动力学的影响

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AbstractCyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus PK in renal transplant patients. CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (−15%), and a trend was observed for everolimus (−7%) and tacrolimus (−16%). Patients carrying at least one CYP3A5*1 allele had 1.5-fold higher tacrolimus clearance compared with noncarriers; however, CYP3A5*3 appeared to be nonpredictive for everolimus and cyclosporine. CYP3A combined genotype did not significantly improve prediction of clearance compared with CYP3A5*3 or CYP3A4*22 alone. These data suggest that dose individualization of cyclosporine, everolimus, or tacrolimus therapy based on CYP3A4*22 is not indicated.CPT: Pharmacometrics Systems Pharmacology (2014); 3, e100; doi:10.1038/psp.2013.78; published online 12 February 2014
机译：摘要环孢素，依维莫司和他克莫司是肾移植免疫抑制治疗的基础。这些药物的特点是治疗窗口狭窄，药代动力学（PK）高度可变以及CYP3A酶的代谢。近来，活性降低的等位基因CYP3A4 * 22被描述为CYP3A4活性的潜在预测标记。这项研究调查了CYP3A4 * 22，CYP3A5 * 3和CYP3A联合基因型对肾移植患者环孢素，依维莫司和他克莫司PK的影响。 CYP3A4 * 22携带者对环孢霉素的清除率显着降低（−15％），依维莫司（−7％）和他克莫司（−16％）观察到趋势。携带至少一种CYP3A5 * 1等位基因的患者，他克莫司清除率比非携带者高1.5倍。然而，CYP3A5 * 3对于依维莫司和环孢菌素似乎是不可预测的。与单独的CYP3A5 * 3或CYP3A4 * 22相比，CYP3A联合基因型没有显着改善清除的预测。这些数据表明未显示基于CYP3A4 * 22的环孢霉素，依维莫司或他克莫司治疗的剂量个体化.CPT：Pharmacometrics Systems Pharmacology（2014）; 3，e100; doi：10.1038 / psp.2013.78; 2014年2月12日在线发布

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