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目的建立静脉注射比伐卢定药代动力/药效学(PK/PD)模型。方法选36名健康受试者,男女各半,随机分为3组,分别单次静脉推注注射用比伐卢定0.50,0.75,1.05 mg.kg-1,在不同时间点监测血药浓度及活性凝血时间(ACT),用WinNonlin软件建立模型。结果比伐卢定静脉注射二房室线性代谢药代动力学模型AIC值最小,药效学用有基础效应的M-M equation模型,建立比伐卢定PK/PD统一模型,模型数理参数分别为Vc=0.12,k10=3.54,k12=0.75,k21=1.44,E0=126.87,Emax=340.03,EC50=4258.03。经验证,不同剂量组比伐卢定PK/PD曲线预测值落在实测值的95%置信区间内,与实测值吻合良好。结论建立的比伐卢定PK/PD模型有较好的适用性。
Objective To establish a pharmacokinetic / pharmacodynamic (PK / PD) model of intravenous injection of bivalirudin. Methods 36 healthy subjects, male and female half, were randomly divided into three groups, respectively, a single intravenous injection of bivalirudin 0.50,0.75,1.05 mg.kg-1, at different time points to monitor plasma concentrations And active coagulation time (ACT), using WinNonlin software to establish the model. Results The bivarious linear metabolic pharmacokinetic model with bivalirudin was the smallest. The pharmacokinetic model of MM equation with basic effect was established. The PK / PD unified model of bivalirudin was established. The model parameters were Vc = 0.12, k10 = 3.54, k12 = 0.75, k21 = 1.44, E0 = 126.87, Emax = 340.03, EC50 = 4258.03. It has been verified that the predicted value of bivalirudin PK / PD curve in different dosage groups falls within the 95% confidence interval of the measured value, which is in good agreement with the measured value. Conclusion The established bivalirudin PK / PD model has good applicability.