丙泊酚注射液在中国成年人中的群体药代动力学研究  

Research on population pharmacokinetics of propofol injection in Chinese adults

作　　者：古安城 许重远[1] 曹婉雯[1] 宿爱山 张建萍[4] 王一丁 秦再生[2] 陈滨[3] GU An-cheng;XU Zhong-yuan;CAO Wan-wen;SU Ai-shan;ZHANG Jian-ping;WANG Yi-ding;QIN Zai-sheng;CHEN Bin(Center of Drug Clinical Trial,Southern Medical University,Guangzhou 510515,Guangdong Province,China;Department of Anesthesiology,Southern Medical University,Guangzhou 510515,Guangdong Province,China;Department of Orthopaedics,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China;College of Pharmacy,Jinan University,Guangzhou 510632,Guangdong Province,China;Department of Obstetrics and Gynecology,The Third Hospital of Southern Medical University,Guangzhou 510630,Guangdong Province,China)

机构地区：[1]南方医科大学南方医院药物临床试验中心,广东广州510515 [2]南方医科大学南方医院麻醉科,广东广州510515 [3]南方医科大学南方医院创伤骨科,广东广州510515 [4]暨南大学药学院,广东广州510632 [5]南方医科大学第三附属医院妇产科,广东广州510630

出　　处：《中国临床药理学杂志》2020年第2期189-192,共4页The Chinese Journal of Clinical Pharmacology

基　　金：广东省教育厅高水平大学建设经费南方医科大学临床研究启动项目基金资助项目(LC2016PY024);广东省科技计划基金资助项目(2017B0200221002)。

摘　　要：目的建立丙泊酚成人群体药代动力学模型,为临床制定个体化给药方案提供参考。方法按入排标准筛选纳入38例受试者,给予2.0 mg·kg^-1丙泊酚,以LC-MS/MS法测定血药浓度,用Sanger测序和焦磷酸测序法对细胞色素酶CYP2B6的G516T(rs3745274)、A785G(rs2279343)位点进行分型,用MONOLIX R2软件建立丙泊酚的群体药代动力学模型。结果静脉给药的三室模型可以很好的描述丙泊酚的药代动力学特征,丙泊酚中央室清除率(CL)、中央室表观分布容积(V)、浅外周室清除率(Q2)、浅外周室表观分布容积(V2)、深外周室清除率(Q3)、深外周室表观分布容积(V3)的群体典型值分别为0.631 L·h^-1,4.08 L,0.885 L·h^-1,6.77 L,0.925 L·h^-1,77.6 L,体重(P<0.01)和性别(P<0.01)对中央室清除率有显著影响。结论本研究建立的丙泊酚群体药代动力学模型稳健有效、具有良好的预测性能,可为临床麻醉时合理用药提供参考。Objective To establish a propofol population pharmacokinetic model and provide a reference for clinical development of individualized modes of administration.Methods According to the inclusion and exclusion criteria,38 subjects were screened and given a dose of 2.0 mg·kg^-1 propofol.The plasma concentration was determined by LC-MS/MS.The two points of G516 T(rs3745274)and A785 G(rs2279343)of CYP2 B6 were typed by Sanger sequencing and pyrosequencing,and the population pharmacokinetic model of propofol was established by MONOLIX R2 software.Results The 3-compartment model is a good model for simulating the pharmacokinetics of propofol.The typical values of propofol central clearance rate,central compartment apparent volume,shallow peripheral compartment clearance,shallow peripheral compartment apparent volume,deep peripheral compartment clearance,and deep peripheral compartment apparent volume were 0.631 L·h^-1,4.08 L,0.885 L·h^-1,6.77 L,0.925 L·h^-1,77.6 L.Conclusion The propofol population pharmacokinetic model established by the study has good predictive performance,which can provide reference for clinical rational drug use.

关 键 词：群体药代动力学 丙泊酚 细胞色素酶P2B6 个体化用药 

分 类 号：R971.2[医药卫生—药品]