Department of Urology, Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, China.
Department of Urology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
World J Pediatr. 2017 Oct;13(5):421-426. doi: 10.1007/s12519-017-0035-4. Epub 2017 May 24.
CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs.
A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Pharmacokinetic-associated parameters such as dose administration, as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the meta-analysis undertaken.
The meta-analysis involved four studies and one study series involving 268 pediatric RTRs. A significant difference was observed in the mean trough concentration/dose of tacrolimus between recipients carrying CYP3A5* 3/3 variants (referred to as "non-expressers") and those carrying CYP3A51 (referred to as "expressers") [standard mean difference (SMD)=-1.09, 95% confidence interval (CI): -1.92 to -0.25, P=0.011]. Moreover, significance was observed in the mean daily dose of tacrolimus between non-expressers and expressers in pediatric RTRs (SMD=0.44, 95% CI: 0.20 to 0.68, P<0.001).
Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.
CYP3A5 基因多态性与成人肾移植中环孢素的药代动力学密切相关。然而，目前尚未有关于 CYP3A5 变异对儿童肾移植受者（RTRs）环孢素剂量需求影响的荟萃分析。我们旨在确定 CYP3A5 多态性对儿童 RTRs 中环孢素药代动力学的影响。
通过检索 PubMed、EMBASE 和 Cochrane 对照试验中心注册库，进行文献检索，纳入相关文章。提取药代动力学相关参数，如剂量给药以及环孢素的浓度和剂量调整浓度，并进行荟萃分析。
荟萃分析涉及四项研究和一项涉及 268 名儿童 RTRs 的研究系列。携带 CYP3A5*3/3 变异（称为“非表达者”）的受者与携带 CYP3A51 的受者（称为“表达者”）之间，环孢素的平均谷浓度/剂量存在显著差异[标准均数差（SMD）=-1.09，95%置信区间（CI）：-1.92 至-0.25，P=0.011]。此外，在儿童 RTRs 中，非表达者与表达者之间，环孢素的平均日剂量也存在显著差异（SMD=0.44，95%CI：0.20 至 0.68，P<0.001）。
我们的荟萃分析表明 CYP3A5 基因型与儿童 RTRs 中环孢素的药代动力学之间存在正相关。
