中国患者异丙酚群体药代动力学(英文)

目的:用NONMEN程序分析中国患者群体药代动力学,并定量研究性别、年龄和体重对异丙酚药代参数的影响。方法:研究了76例择期手术的患者(男37例、女39例、年 龄19-77岁、体重39-86kg),共收集1459个血液标本。用NONMEN方法分析清除率和分布容积的个体间变异以及年龄、体重和性别的影响。结果:可用三室模型模拟异丙酚的药代动力学参数。体重可影响异丙酚的中央室、浅外周室和深外周室的清除率以及中央室的分布容积,而浅外周室和深外周室的分布容积保持不变。体重60kg的成人的上述药代参数的估计值分别为:1.56L/min、0.737L/min、0.360L/min、12.1L、43L、213L。老人随年龄的增大而清除率和中央室的分布容积减少。结论:中国人的异丙酚的药代动力学可用标准三室模型描述,年龄和体重可影响模型参数。因此根据患者的个体药代参数可改善靶控输注的精密度。

Population pharmacokinetics of propofol in Chinese patients

AIM:To analyze population pharmacokinetics of propofol in Chinese surgical patients using a nonlinear mixedeffect model (NONMEM) program and to quantitate the effects of covariance of gender, age, and body weight. METHODS: The population pharmacokinetics of propofol was investigated in 76 selective surgical patients (37 males and 39 females aged 19-77a, weighing 39-86kg). A total of 1439 blood samples were analyzed using NONMEM(NONMEM Projeft Group, University of California, San Francisco, CA). Interindividual variability was estimated fro clearances and distribution volumes. The effects of age, body weight, and gender were in vestigated. RESULTS: The pharmacokinetics of propofol in Chinese patients was best described by a three-compartment pharmacokinetic model. Body weight was found to be a significant factor for the elimination clearance, the two inter-compartmental clearances, and the volume of the central compartment. The volumes of the shallow peripheral compartment and deep peripheral compartment remain constant for all individuals. The estimates of these parameters for a 60-kg adult were 1.56L/min, 0.737L/min, 0.360L/min, 12.1L, 43L, and 213L, respectively. For old patients, the elimination clearance and volume of the central compartment decreased. CONCLUSION:The pharmacokinetics of propofol in Chinese patients can be well described by a standard three-compartment pharmacokinetic model. Inclusion of age and body weight as covariances significantly improved the model. Adjusting pharmacokinetics to the individual patients should improve the precision of target-controlled infusion system.