细胞色素P4503A5基因多态性对二氢吡啶类钙拮抗剂药代动力学影响的Meta分析  

Effect of Cytochrome P4503A5 Gene Polymorphism on the Pharmacokinetics of Dihydropyridine Calcium Antagonists:a Meta-analysis

作　　者：李珍[1] 王思扬 任健 朱园园 冯金鑫 张瑞琴[2] LI Zhen;WANG Siyang;REN Jian;ZHU Yuanyuan;FENG Jinxin;ZHANG Ruiqin(Shanxi Medical University,Taiyuan 030001,Shanxi,China;Second Hospital of Shanxi Medical University,Taiyuan 030000,Shanxi,China)

机构地区：[1]山西医科大学,太原030001 [2]山西医科大学第二医院,太原030000

出　　处：《中西医结合心脑血管病杂志》2021年第3期396-401,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：山西省自然科学基金资助项目(No.201801D121221)。

摘　　要：目的系统评价细胞色素P4503A5(CYP3A5)基因多态性对二氢吡啶类钙拮抗剂药代动力学的影响。方法检索PubMed、Wiley Online Library、Cochrane Library、EMbase、万方数据库、中文科技期刊全文数据库(VIP)、中国学术期刊全文数据库(CNKI),收集各数据库建库至2020年4月5日发表的有关CYP3A5基因多态性对二氢吡啶类钙拮抗剂药代动力学影响的文献,提取血药浓度-时间曲线下面积(AUC0-t)、峰浓度(Cmax)、表观清除率(CL/F)和半衰期(t1/2)等药代动力学参数,应用RevMan 5.3软件对纳入研究文献进行Meta分析,比较野生杂合子基因型(AA,*1/*1)、突变杂合子基因型(AG,*1/*3)和突变纯合子基因型(GG,*3/*3)的差异。结果最终共纳入6篇文献进行Meta分析,涉及252例病人。Meta分析结果显示,CYP3A5*1/*3突变杂合子型与CYP3A5*3/*3突变纯合子型相比,Cmax差异有统计学意义[SMD=-0.41,95%CI(-0.81,-0.00),P=0.05],基因型CYP3A5*1携带者与基因型CYP3A5*3携带者相比,CL/F[SMD=-0.41,95%CI(-0.71,-0.11),P=0.007]和t1/2[SMD=0.49,95%CI(0.21,0.77),P=0.0006]差异均有统计学意义,其余基因型对二氢吡啶类钙拮抗剂的药代动力学影响比较差异无统计学意义。结论现有证据表明,CYP3A5基因多态性对二氢吡啶类钙拮抗剂的药代动力学存在影响,CYP3A5*3/*3突变型人群的二氢吡啶类钙拮抗剂CL/F、Cmax减小、t1/2延长,代谢减慢。本Meta分析结果对临床用药安全性和有效性有一定借鉴意义。Objective To systematically evaluate the effect of cytochrome P4503A5(CYP3A5)gene polymorphism on the pharmacokinetics of dihydropyridine calcium antagonists.Methods PubMed,Wiley Online Library,Cochrane Library,EMbase,Wanfang Database,Full-text Database of Chinese sci-tech journals(VIP),and Full text Database of Chinese academic journals(CNKI)were searched from the establishment to April 5,2020 for the relationship between CYP3A5 gene polymorphism and the pharmacokinetics of dihydropyridine calcium antagonists.Pharmacokinetic parameters such as area under the blood concentrate-time curve(AUC0-t),peak concentration(Cmax),epigenetic clearance rate(CL/F),and half-life(t1/2)were extracted.Meta-analysis was performed by Rev Man 5.3 software to compare the differences between wild heterozygous genotypes(AA,*1/*1),mutant heterozygous genotypes(AG,*1/*3)and mutant homozygous genotypes(GG,*3/*3).Results Six literatures were included,involving 252 patients.The result of Meta-analysis showed that of compared with mutant homozygous CYP3A5*3/*3,Cmax mutant heterozygous CYP3A5*1/*3 had statistically significant differences[SMD=-0.41,95%CI(-0.81,-0.00),P=0.05].Compared with CYP3A5*3 carriers with genotype CYP3A5*3 carriers,CL/F[SMD=-0.41,95%CI(-0.71,-0.11),P=0.007]and t1/2[SMD=0.49,95%CI(0.21,0.77),P=0.0006],the differences were statistically significant.The other genotypes had no significant effect on the pharmacokinetics of dihydropyridine calcium antagonists.Conclusion Current evidence showed that the polymorphism of CYP3A5 gene had an effect on the pharmacokinetics of dihydropyridine calcium antagonists.In CYP3A5*3/*3 mutant population,CL/F and Cmax of dihydropyridine calcium antagonists decreased,T1/2 increased,and metabolism slow down,which had certain reference significance for the safety and effectiveness of clinical medication.

关 键 词：二氢吡啶类钙拮抗剂 细胞色素P4503A5 基因多态性 药代动力学 META分析 

分 类 号：R96[医药卫生—药理学]