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...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 metaanalysis 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 nonexpressers 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.展开更多
基金grants from the National Natural Science Foundation of China(81570676,81100532,81470981).The Science and Education Health Project of Jiangsu Province for Important Talent(RC2011055).The'333 High Level Talents Project'in Jiangsu Province(2011 and 2013).The Jiangsu Province Six Talents Peak from Department of Human Resources,Social Security Office of Jiangsu Province of China(2010WSN-56,2011-WS-033).The General Program of Department of Health of Jiangsu Province of China(H2009907).The Priority Academic Program Development of Jiangsu Higher Education Institutions(JX10231801).
文摘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 metaanalysis 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 nonexpressers 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.
