CYP2A6~* 4基因多态性对右美托咪定药动学的影响  

Effects of CYP2A6~* 4 gene polymorphism on dexmedetomidine pharmacokinetics

作　　者：冯淑玲[1,2] 王凌 王少明[1,2] 庄捷 齐娟[2,3] 于荣国 FENG Shuling;WANG Ling;WANG Shaoming;ZHUANG Jie;QI Juan;YU Rongguo(Department of Pharmacy,Fujian Provincial Hospital;Provincial Clinical College of Fujian Medical University;Second Department of Anesthesiology,Fujian Provincial Hospital;Surgery Intensive Care Unit,Fujian Provincial Hospital,Fuzhou 350001,Fujian,China)

机构地区：[1]福建省立医院药学部 [2]福建医科大学省立临床医学院 [3]福建省立医院麻醉二科 [4]福建省立医院重症外科

出　　处：《中国临床药理学与治疗学》2018年第12期1368-1372,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:在CYP2A6~*4突变频率高的中国人中测定CYP2A6~*4等位基因对右美托咪定药代动力学的影响,为临床提供参考。方法:31名手术患者通过静脉泵接受0.5μg/kg右美托咪定后,抽取多个时间点的血样,测定血药浓度以及CYP2A6~*4的多态性,并进行统计分析。结果:9名患者为~*1/~*4或~*4/~*4,22名患者为~*1/~*1。主要药代动力学参数如下,曲线下面积(AUC)为(1 396.19±332.47)h·ng·L^(-1),峰值血药浓度(C_(max))为(495.50±104.90)ng/L,分布容积(V)为(0.68±0.20)L/kg,清除率(CL)为(0.38±0.11)L·h^(-1)·kg^(-1),分布半衰期(t_(1/2α))为(0.05±0.01)h,消除半衰期(t_(1/2β))为(2.53±0.04)h。在CYP2A6~*1/~*1,~*1/~*4和~*4/~*4患者中未发现显著的药代动力学差异。结论:中国患者使用右美托咪定后,t_(1/2β)与公布的一致,但t_(1/2α),V和CL较低。在制定右美托咪定的精准治疗方案时,可不予考虑CYP2A6~*4突变。AIM:To determine the dexmedetomidine pharmacokinetics of CYP2A6*4 allele in Chinese patients with high mutation frequency of CYP2A6*4 in order to provide clinical references.METHODS:Thirty-one surgery patients received 0.5μg/kg dexmedetomidine via intravenous pump.Their plasma concentrations at multiple time-points and polymorphism of CYP2A6*4 were determined and statistically analyzed.RESULTS:Nine patients were*1/*4 or*4/*4,and 22 patients were*1/*1.The main pharmacokinetic parameters were area under curve(AUC)(1 396.19±332.47)h·ng·L-1,peak blood concentration(C max)(495.50±104.90)ng/L,distribution volume(V)(0.68±0.20)L/kg,clearance(CL)(0.38±0.11)L·h-1·kg-1,distribution half-life(t 1/2α)(0.05±0.01)h,elimination half-life(t 1/2β)(2.53±0.04)h.No significant pharmacokinetic differences were found among CYP2A6*1/*1,*1/*4,and*4/*4 patients.CONCLUSION:In Chinese patients treated with dexmedetomidine,t 1/2βis consistent with that published,but t 1/2α,V and CL are lower.It is unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.

关 键 词：右美托咪定 CYP2A6 药动学 基因多态性 

分 类 号：R614[医药卫生—麻醉学] R969.1[医药卫生—外科学]