雷贝拉唑抑制胃酸分泌的药动学-药效学结合研究  

Combined Pharmacokinetics-pharmacodynamics Study of Rabeprazole in Inhibition of Gastric Acid Secretion

作　　者：袁红宇 王永庆 张宏文 孟玲 郝琨[3] 

机构地区：[1]江苏盛泽医院药剂科,吴江215228 [2]南京医科大学第一附属医院药学部,南京210029 [3]中国药科大学药物代谢与动力学研究中心,南京210009

出　　处：《医药导报》2014年第6期699-702,共4页Herald of Medicine

基　　金：江苏省卫生厅医学科技发展基金临床药学研究科技项目(P200808)

摘　　要：目的应用药动学与药效学(PK-PD)结合模型,研究雷贝拉唑抑制胃酸分泌的药动学与药效学过程。方法给10例健康受试者静脉滴注雷贝拉唑20 mg,高效液相色谱法测定不同时间点血浆雷贝拉唑浓度,DAS 2.0版软件计算药动学参数;同时监测24 h胃内pH,采用间接反应药效抑制的PK-PD结合模型对药效学参数进行拟合。结果雷贝拉唑在健康受试者体内的主要药动学参数t1/2为(60.5±17.3)min、Cmax为(1 299.1±201.0)ng·mL-1、AUC0-τ为(106.4±26.0)mg·min·L-1。间接反应抑制模型拟合的主要药效学参数分别为Kin=(8.200±3.362)h-1,Ke=(1.080±0.378)h-1,IC50=(0.286±0.129)mg·L-1,Imax=(6.93±2.15)(以pH计)。结论雷贝拉唑在健康志愿者体内药动学符合一房室静脉滴注模型,药效学过程符合间接反应抑制结合模型的特征,用该模型计算得到的方程能有效建立起雷贝拉唑血药浓度与效应间的对应关系。Objective To investigate the pharmacokinetics （PK） and pharmacodynamics （PD） processes of rabeprazole in inhibiting gastric acid secretion with the combined PK-PD model. Methods A total of 10 healthy volunteers were given a intravenous infusion of 20 mg rabeprazole over a 30-min period. The concentration of rabeprazole in the plasma at different time points was detected by HPLC, and the PK parameters were calculated by DAS 2.0 software. At the same time the intragastric pH was monitored over 24 hours to fit the PD parameters with indirect inhibition model. Results The main PK parameters,t1/2 ,Cmax,and AUC were （60.5±17.3） min, （1 299.1±201.0） ng · mL^-l ,and （106.4±26.0） mg ·min · L^-1, respectively. The corresponding PD parameters ,Kin ,Ke ,IC50 and /max were （8. 200±3. 362 ） h^-1, （ 1. 080±0. 378 ） h^-1 , （0. 286±0. 129） mg · L^-1 and （6.93± 2.15 ） pH, respectively. Conclusion The PK of rabeprazole in healthy volunteers conforms to one eompartment model, and the PD fits the indirect response inhibition model. The equation can effectively establish the relationship between the blood drug concentration and the effect.

关 键 词：雷贝拉唑 药动学-药效学结合 抑制模型 间接反应 

分 类 号：R975[医药卫生—药品] R969.1[医药卫生—药学]