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

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.