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目的 运用非线性混合效应模型(NONMEM)软件计算国人异丙酚靶控输注(TCI)群体药代动力学参数并分析药代动力学特点。方法 61例行择期手术患者,ASAⅠ～Ⅱ级,男26例,女35例,年龄18～64岁,体重41～83kg。采用Tackley药代动力学参数,恒定靶血浆药物浓度(3μg·ml~(-1))变速输注60min,间断采血90min,共976个血标本,用气相色谱-质谱法测定异丙酚的血浆药物浓度。运用NONMEM软件估算异丙酚TCI群体药代动力学参数并分析药代动力学变化特点。结果 国人异丙酚TCI可用二室开放型药代动力学模型进行描述。最终药代动力学参数:K_(10)、K_(12)、K_(21)分别为0.111、0.064、0.023min~(-1);V_1、V_2分别为0.205、0.404L·kg~(-1);CL_1、CL_2分别为22.76、13.24ml·min~(-1)·kg~(-1)。最终回归模型中异丙酚血药浓度估算值与实测浓度间线性关系良好。在固定效应参数中,体重影响V_1、CL_1,年龄影响K_(21),性别对参数无影响。结论 国人异丙酚TCI的药代动力学特点为可用二室指数开放模型进行描述,中央室分布容积明显小于欧美人群,药物从中央室向外周室转运和消除速率较快。
Objective To calculate the pharmacokinetic parameters of propofol target-controlled infusion (TCI) in Chinese population by using NONMEM software and analyze the pharmacokinetic characteristics. Methods Totally 61 patients undergoing elective surgery, ASA Ⅰ ~ Ⅱ grade, 26 males and 35 females, aged 18 to 64 years old, weighing 41 to 83kg. Tackley pharmacokinetic parameters, constant target plasma drug concentration (3μg · ml ~ (-1)) infusion for 60min, intermittent blood collection 90min, a total of 976 blood samples were determined by gas chromatography-mass spectrometry propofol plasma Drug concentration. Pharmacokinetic parameters of the propofol TCI population were estimated using NONMEM software and the pharmacokinetic changes were analyzed. Results Propofol TCI can be described by a two-compartment open-ended pharmacokinetic model. The final pharmacokinetic parameters were as follows: K_ (10), K_ (12) and K_ (21) were 0.111,0.064,0.023min -1; V_1 and V_2 were 0.205,0.404L · kg -1 ); CL_1 and CL_2 were 22.76 and 13.24 ml · min -1 (-1) kg -1 respectively. In the final regression model, there was a good linear relationship between the estimated plasma concentration of propofol and the measured concentration. In the fixed effect parameters, body weight affected V_1, CL_1, age affected K_ (21), gender had no effect on the parameters. Conclusions The pharmacokinetics of propofol TCI in Chinese people can be described by two-compartment open model. The distribution volume of central ventricle is obviously smaller than that in Europe and the United States. The transport and elimination rate of drug from central ventricle to peripheral ventricle is faster.