丙泊酚注射液在成年全麻患者中的群体药代动力学研究  

Research on population pharmacokinetics of propofol injection in adult patients under general anesthesia

作　　者：李金霞 古安城 袁福淼 李偲[3] 邓海军[4] 许重远[1,2] LI Jin-xia;GU An-cheng;YUAN Fu-miao;LI Cai;DENG Hai-jun;XU Zhong-yuan(Clinical Pharmacy Center,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China;National Medical Products Administration Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,Guangdong Province,China;Department of Anesthesiology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China;Department of General Surgery,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]南方医科大学南方医院,临床药学中心,广东广州510515 [2]南方医科大学国家药品监督管理局药物代谢研究与评价重点实验室及广东省新药筛选重点实验室,广东广州510515 [3]南方医科大学南方医院,麻醉科,广东广州510515 [4]南方医科大学南方医院,普外科,广东广州510515

出　　处：《中国临床药理学杂志》2024年第14期2124-2128,共5页The Chinese Journal of Clinical Pharmacology

基　　金：南方医科大学南方医院临床研究专项基金资助项目(2019CR015)。

摘　　要：目的定量考察不同因素对于丙泊酚药代动力学参数的影响,构建适用于中国患者的丙泊酚群体药代动力学模型。方法纳入30例择期进行腹部手术的患者用丙泊酚2.0 mg·kg^(-1)进行麻醉给药,用液相色谱-质谱联用分析技术对采集的静脉血样本进行血药浓度测定,用一代测序技术Sanger法对代谢酶基因多态性进行检测,用Phoenix软件进行药代动力学参数的计算、模型构建及评价分析。结果经软件分析,用三房模型描述药物的体内过程,计算参数中央室清除率(CL)、浅外周室清除率(Q_(2))、深外周室清除率(Q_(3))、中央室分布容积(V)、浅外周室分布容积(V_(2))、深外周室分布容积(V_(3))群体均值分别为1.71 L·min^(-1)、1.31 L·min^(-1)、1.51 L·min^(-1)、5.92 L、19.86 L、99.06 L,体质量作为对CL和V有显著影响的协变量纳入到模型中。结论对最终模型进行评估显示模型具有较好的预测能力,可为临床中丙泊酚的使用提供方向性建议。Objective To quantitatively assess the influence of various factors on the pharmacokinetic parameters of propofol and to develop a propofol population pharmacokinetic model tailored for Chinese patients.Methods Thirty patients scheduled for selective abdominal surgeries received an anesthesia dose of propofol at 2.0 mg·kg^(-1).The concentration of propofol in collected venous blood samples was measured using liquid chromatography-tandem mass spectrometry.Polymorphisms in metabolizing enzyme genes were detected through Sanger sequencing technology.Pharmacokinetic parameters were computed,and models were constructed and evaluated using Phoenix Winnonlin software.Results Through software analysis,the drug's in vivo process was best described by a three-compartment model.The population mean values for the central compartment clearance rate(CL),shallow peripheral compartment clearance rate(Q_2),deep peripheral compartment clearance rate(Q_(3)),central compartment volume of distribution(V),shallow peripheral compartment volume of distribution(V_(2)),and deep peripheral compartment volume of distribution(V_(3))were 1.71 L·min^(-1),1.31 L·min^(-1),1.51 L·min^(-1),5.92 L,19.86 L and 99.06 L,respectively.Body weight was identified as a significant covariate affecting CL and V,and was incorporated into the model.Conclusion The evaluation of the final model demonstrates its substantial predictive capability,offering directional guidance for the clinical administration of propofol.

关 键 词：丙泊酚 群体药代动力学 个体化给药 基因多态性 

分 类 号：R971.2[医药卫生—药品]