靶控输注丙泊酚时的瑞芬太尼群体药代动力学

摘要

Objective The study is to develop a population pharmacokinetic model of remifentanil, and to evaluate effects of covariates on the pharmacokinetics in Chinese patients. Methods Fifty patients (ASA grade I or Ⅱ , undergoing elective surgery, aged 25 to 93 years old) were randomly divided into two remifentanil infusion scheme of 0.3 pig · kg-1 · min-1 and 0.6 M8·kg-1·min-1 until the end of surgery. Frequent arterial blood samples were drawn according to predetermined time and assayed for remifentanil concentration. Nonlinear mixed-effects modeling was used to evaluate the time courses of the measured concentrations. Results The pharmacokinetic data of remifentanil were well described using a three-compartment linear model with first-order elimination from the central compartment. Gender and age were significant factors of central compartment (V1) and deep peripheral compartment (V3 ), respectively. The other covariates including bodyweight (WT), gender, lean body mass (LBM), body mass index (BMI) and body surface area (BSA) did not influence the pharmacokinetics of remifentanil. For typical patient. PK parameters were: Vi 8. 76 L for male, 5. 1 L for female, V2 5. 93 L, V3 4. 90 L, Cl1, 2. 86 L/min, Cl2 1. 36 L/min, Cl3 0. 23 L/min. Conclusion The pharmacokinetics of remifentanil is consistent with its rapid elimination by blood and tissue esterase in Chinese patients. The central volume of female was about 42% lower than that of male. Age was a determinant of the volume of slow peripheral compartment. Bodyweight, LBM, BMI and BSA have no effect on pharmacokinetics of reminifentaniL%目的 建立靶控输注丙泊酚时的瑞芬太尼群体药代动力学,并探索协变量的影响.方法 全麻择期手术患者50例,年龄25～93岁,27例患者持续输注瑞芬太尼0.3 μg· kg-1·min-1或23例患者0.6 μg·kg-1 ·min-1.采集动脉血分析血药浓度,NONMEM分析建立群体药代动力学模型.结果 瑞芬太尼药代动力学适合用三室模型描述,性别和年龄显著影响中央室容积(V1)和深外周室容积(V3),瘦体重(LBM)、体表面积(BSA)和体重指数(BMI)不影响其药代动力学.患者瑞芬太尼药代动力学参数典型值为V18.76 L(男)、5.10 L(女),浅外周室容积(V2) 5.93 L,V3 4.90 L,系统清除率(CL1)2.86 L/min,浅外周室清除率(CL2)0.70 L/min,深外周室清除率(CL3)0.23L/min.结论 瑞芬太尼的药代动力学特点与其经血液和组织酯酶迅速水解的特点一致.女性V1比男性低42%,V3与年龄有关,体重、LBM、BSA和BMI不影响瑞芬太尼的药代动力学参数.