Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies.
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.
['Zong|Yi-Ping|YP|', 'Wang|Zi-Jie|ZJ|', 'Zhou|Wan-Li|WL|', 'Zhou|Wei-Min|WM|', 'Ma|Tie-Liang|TL|', 'Huang|Zheng-Kai|ZK|', 'Zhao|Chun-Chun|CC|', 'Xu|Zhen|Z|', 'Tan|Ruo-Yun|RY|', 'Gu|Min|M|']
D002648:Child D051544:Cytochrome P-450 CYP3A D006801:Humans D007166:Immunosuppressive Agents D016030:Kidney Transplantation D064887:Observational Studies as Topic D020641:Polymorphism, Single Nucleotide D016559:Tacrolimus
CYP3A5 tacrolimus pediatric kidney transplantation meta-analysis