Effect of CYP3A5*1 expression on tacrolimus required dose for transplant pediatrics: A systematic review and meta-analysis

This systematic review was designed to find out optimal tacrolimus dose in pediatrics according to their CYP3A5*1 genotype by performing meta-analysis. PubMed, Scopus, ISI web of Science, ProQuest, Cochrane library, and clinicaltrail.gov were systematically searched to find studies in which tacrolimus dose and/or blood concentration and/or concentration-to-dose (C/D) ratio were determined in genotype groups of CYP3A5*1 in pediatric population. Data were extracted at 14 time points post-transplantation and meta-analysis of mean and SD was performed. In all, 11 studies including 596 pediatric transplant recipients were entered into systematic review and meta-analysis. Analysis of tacrolimus required dose, blood concentration, and C/D ratio in 14 time points post-transplantation resulted in significant differences between expressers and non-expressers of CYP3A5*1. It seems that 0.06 mg/kg/day higher tacrolimus dose in expressers can produce same blood level as non-expressers. Using results of TDM for tacrolimus dose adjustment, it takes about 1 month for patients to reach stable and optimum tacrolimus blood concentration. This is too long time period which increases the risk of immunosuppressive over/under-dose and drug toxicity or organ rejection. Considering our results, defining genetic profile helps to predict the individual required dose more rapidly, actually before beginning of treatment.