多药耐药基因1（MDR1）C1236T多态性对环孢素药代动力学的影响：一项系统评价和荟萃分析。
Effect of MDR1 C1236T polymorphism on cyclosporine pharmacokinetics: A systematic review and meta-analysis.
作者信息
Chen Zhe, Zhang Lingli, Yang Chunsong, Jiang Zhimei, Shen Hongxin, Gui Ge
机构信息
Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
出版信息
Medicine (Baltimore). 2017 Nov;96(47):e8700. doi: 10.1097/MD.0000000000008700.
BACKGROUND
Cyclosporine (CsA) is one of the immunosuppressive drugs, whose pharmacokinetic characteristics vary greatly among individuals. The published data reveal conflicting effects of the polymorphism of MDR1 exon 12 SNP C1236T on the pharmacokinetics of cyclosporine.This study aims to conduct a meta-analysis to investigate the effect of SNP C1236T on the pharmacokinetics of cyclosporine.
METHODS
A literature retrieval was conducted to find the relevant papers in databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) electronic source for published studies until January 2017. The pharmacokinetic parameters, including C0 (trough blood concentration), C2 (whole-blood levels at 2 hours after drug intake), Cmax (the maximum concentration), and daily dose were extracted and a meta-analysis was performed by RevMan 5.3.
RESULTS
A total of 11 papers concerning 1361 individuals were included in the meta-analysis. As for dose adjusted C0, the results showed difference between subjects carrying CC genotypes and TT genotypes (MD: 6.76, 95% CI [2.38, 11.14], P = .02]. As for C2, the results showed significant difference between subjects carrying CC genotypes and CT genotypes (MD: -18.50, 95% CI [-35.49, -1.52], P = .03), as well as CC genotypes and TT genotypes (MD: -19.01, 95% CI (-35.85, -2.16), P = .03). As for Cmax, daily dose, and C0, the overall results showed no major influence.
CONCLUSIONS
MDR1 C1236T polymorphism may have a minor effect on cyclosporine pharmacokinetics in transplantation patients.
背景
环孢素（CsA）是免疫抑制药物之一，其药代动力学特征在个体间差异很大。已发表的数据显示，多药耐药基因1（MDR1）外显子12单核苷酸多态性（SNP）C1236T对环孢素药代动力学的影响存在矛盾。本研究旨在进行一项荟萃分析，以探讨SNP C1236T对环孢素药代动力学的影响。
方法
进行文献检索，在包括PubMed、Embase、Cochrane图书馆、中国知网（CNKI）、万方数据库（万方）、中国生物医学文献数据库（CBM）、维普中文科技期刊数据库（VIP）等数据库中查找截至2017年1月发表的相关研究。提取药代动力学参数，包括C0（谷血药浓度）、C2（服药后2小时全血浓度）、Cmax（最大浓度）和每日剂量，并使用RevMan 5.3进行荟萃分析。
结果
荟萃分析共纳入11篇涉及1361名个体的论文。对于剂量调整后的C0，结果显示携带CC基因型和TT基因型的受试者之间存在差异（MD：6.76，95%CI[2.38，11.14]，P = 0.02）。对于C2，结果显示携带CC基因型和CT基因型的受试者之间存在显著差异（MD：-18.50，95%CI[-35.49，-1.52]，P = 0.03），以及携带CC基因型和TT基因型的受试者之间也存在显著差异（MD：-19.01，95%CI[-35.85，-2.16]，P = 0.03）。对于Cmax、每日剂量和C0，总体结果显示无重大影响。
结论
MDR1 C1236T多态性可能对移植患者中环孢素的药代动力学有轻微影响。
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