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首页> 外文期刊>Therapeutic Drug Monitoring >A systematic review of the effect of CYP3A5 genotype on the apparent oral clearance of tacrolimus in renal transplant recipients.
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A systematic review of the effect of CYP3A5 genotype on the apparent oral clearance of tacrolimus in renal transplant recipients.

机译：CYP3A5基因型对他克莫司在肾移植受者中的口服口服他克莫司清除的影响的系统评价。

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摘要

Tacrolimus is a commonly used immunosuppressive agent in renal transplantation. Therapeutic drug monitoring of tacrolimus is recommended because it demonstrates wide pharmacokinetic interpatient variability. Part of that variability may be the result of metabolism by cytochrome P450 3A5 (CYP3A5), which is only expressed in some adult individuals. The expression of CYP3A5 has been linked to the CYP3A5 genotype, in which individuals with one or more wild-type allele (CYP3A5*1) are considered CYP3A5 expressors, and individuals homozygous for the mutant allele CYP3A5*3 are considered nonexpressors. An association has been established between CYP3A5 genotype (expressors versus nonexpressors) and tacrolimus dose requirements to achieve target concentrations. Tacrolimus pharmacokinetic variability is based on bioavailability and systemic clearance, which are represented by apparent oral clearance. The focus of this review was to use a systematic method to investigate whether the CYP3A5 genotype has an effect on the apparent oral clearance of tacrolimus in renal transplant recipients. A total of five studies were identified that reported apparent oral clearance in CYP3A5 expressors and CYP3A5 nonexpressors. The weighted mean apparent oral clearance was found to be 48% lower in CYP3A5 nonexpressors than CYP3A5 expressors (range, 26%-65%). This difference in apparent oral clearance could be used in future studies to guide initial dosing strategies of tacrolimus in renal transplant recipients based on genotype.
机译：他克莫司是肾移植中常用的免疫抑制剂。建议对他克莫司进行治疗性药物监测，因为它证明了患者之间的药代动力学差异很大。这种可变性的部分原因可能是细胞色素P450 3A5（CYP3A5）的代谢所致，其仅在某些成年个体中表达。 CYP3A5的表达已与CYP3A5基因型相关联，其中具有一个或多个野生型等位基因（CYP3A5 * 1）的个体被视为CYP3A5表达子，而具有突变等位基因CYP3A5 * 3的纯合子被视为非表达子。 CYP3A5基因型（表达子与非表达子）与他克莫司的剂量要求之间存在关联，以达到目标浓度。他克莫司的药代动力学变异性是基于生物利用度和全身清除率，其表现为明显的口服清除率。这篇综述的重点是使用一种系统的方法来研究CYP3A5基因型是否对他克莫司在肾脏移植接受者中的口服他克莫司的表观清除率有影响。共鉴定出五项研究，这些研究报告了CYP3A5表达子和CYP3A5非表达子的明显口腔清除率。发现CYP3A5非表达者的加权平均表观口腔清除率比CYP3A5表达者低48％（范围为26％-65％）。这种明显的口腔清除率差异可用于将来的研究中，以根据基因型指导他克莫司在肾移植受者中的初始给药策略。

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