摘要
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 the PK/PD model of bivalirudin injection in Chinese healthy population.Methods Thirty-six Chinese healthy volunteer were selected and enrolled in 3 groups randomly.Each group was administrated bivalirudin by 0.50,0.75,1.05 mg·kg-1 iv bolus once respectively.Plasma drug concentration and activated clotting time（ACT） were measured at different time,and then PK/PD model of bivalirudin was established by WinNonlin program.Results According to the stimulating of the bivalirudin compartment model,the value of AIC is minimum in the two-compartment model.The pharmacodynamic model fit the M-M equation model.The parameters of the PK/PD model are as follows： Vc=0.12,k10=3.54,k12=0.75,k21=1.44,E0=126.87,Emax=340.03,EC50=4258.03.All the model value lies in the 95% confidence interval.Conclusion The developed PK/PD model of bivalirudin can predict the clinical effect accurately in Chinese.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2012年第9期677-679,共3页
The Chinese Journal of Clinical Pharmacology
