Yi-Ping Zong1,2, Zi-Jie Wang1, Wan-Li Zhou1, Wei-Min Zhou2, Tie-Liang Ma3, Zheng-Kai Huang1, Chun-Chun Zhao1, Zhen Xu1, Ruo-Yun Tan1, Min Gu4. 1. Department of Urology, Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, China. 2. Department of Urology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China. 3. Central Laboratory, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China. 4. Department of Urology, Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, China. Lancetgu@aliyun.com.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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 CYP3A5*1 (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). CONCLUSION: Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.
BACKGROUND: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. METHODS: 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. RESULTS: 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 CYP3A5*1 (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). CONCLUSION: Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.
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