Hendijani Fatemeh, Azarpira Negar, Kaviani Maryam
Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Faculty of Pharmacy, Department of Pharmacognosy and Pharmaceutical Biotechnology, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Pediatr Transplant. 2018 Jun 19:e13248. doi: 10.1111/petr.13248.
This systematic review was designed to find out optimal tacrolimus dose in pediatrics according to their CYP3A51 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 CYP3A51 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.
本系统评价旨在通过荟萃分析找出根据儿童CYP3A51基因型确定的他克莫司最佳剂量。系统检索了PubMed、Scopus、科学引文索引（ISI）数据库、ProQuest、考克兰图书馆和ClinicalTrials.gov，以查找在儿童人群的CYP3A51基因型组中测定他克莫司剂量和/或血药浓度和/或浓度-剂量（C/D）比的研究。在移植后14个时间点提取数据，并对均值和标准差进行荟萃分析。共有11项研究（包括596名儿童移植受者）纳入系统评价和荟萃分析。对移植后14个时间点的他克莫司所需剂量、血药浓度和C/D比进行分析，结果显示CYP3A5*1表达者和非表达者之间存在显著差异。似乎表达者使用比非表达者高0.06mg/kg/天的他克莫司剂量可产生相同的血药水平。利用他克莫司血药浓度监测（TDM）结果调整剂量，患者达到稳定且最佳的他克莫司血药浓度约需1个月。这一时间过长，增加了免疫抑制剂量过量/不足以及药物毒性或器官排斥的风险。根据我们的研究结果，确定基因谱有助于在治疗开始前更快速地预测个体所需剂量。
