用计算机模拟选择丙泊酚的药代动力学参数

Selection of pharmacokinetic parameter set of propofol with computer simulation

目的 用Marsh、Shuttler和Kirkpatrick(以下简称M、S、K参数)报道的药代学参数模拟单次静注丙泊酚血浆浓度以选择适合中国人的参数。方法 90例患者分为青年组、中年组和老年组,测定和模拟静注丙油酚后1～5 min和10 min血浆浓度。计算样本加权残差(WR)和绝对值加权残差(absWR)、个体内中位数加权残差(MDWR)和中位数绝对值加权残差(MDAWR)、预测和实测浓度的目标函数。结果 三种参数预测和实测浓度均显著相关(P<0.05)。老年组M和S参数WR、absWR、MDWR、MDAWR无差异,但与K参数差异显著(P<0.05);中、青年组S参数预测和实测浓度拟合最好。老、中和青年组Marsh参数目标函数分别是-286.9、-332.2和-480.5,S参数分别是-290.6、-334.6和-393.5,K参数分别是-454.7、-350.2和-386.6。结论 M和S药代学参数适用于老年人单次静注丙泊酚浓度预测,中青年选用S参数为好。

Objective Using three pharmacokinetic parameter sets reported by Marsh, Schuttler and Kirkpatrick to simulate the plasma concentration of propofol after bolus injection so as to select pharmacokinetic parameter set fitting for Chiness. Methods Ninety patients were divided into young group, middle age group and elderly group. Plasma concentration of propofol was measured and simulated at 1-5 min and 10 min after bolus. Weight residuals (WR) and absolute WR, median weight residu-als(MDWR)and median absolute weight residuals (MDAWR), objection functions were calculated. Results Predicted concentrations of three parameter sets were significantly related to measured concentrations(P<0. 05). WR,absWR,MDWR and MDAWR were similar between Marsh and chut-tler parameter set in elderly group, but them were different significantly compared with Kirkpatrick parameter set(P<0. 05). Predicted concentrations with Schuttler parameter set have best goodness of fit in middle age group and young group. Objection functions of Marsh parameter set were -286. 9, -332. 2, -480. 5 in elderly group, middle age group and young group respectively, relevant values with Schuttler and Kirkpatrick parameter set were -290. 6, -334. 6, -393. 5 and -454. 7, -350. 2, -386. 6. Conclusion Pharmacokinetic parameter sets of propofol reported by Marsh and Schuttler are fitting to predict plasma concentration in elderly Chinese. But it is best to select parameter set reported by Schuttler in middle-aged and young Chinese.