CAJ | 학술논문

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（1299.1±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。
목적：응용약동학여약효학（ PK-PD）결합모형，연구뢰패랍서억제위산분비적약동학여약효학과정。방법급10례건강수시자정맥적주뢰패랍서20 mg，고효액상색보법측정불동시간점혈장뢰패랍서농도，DAS 2.0판연건계산약동학삼수；동시감측24 h위내pH，채용간접반응약효억제적PK-PD결합모형대약효학삼수진행의합。결과뢰패랍서재건강수시자체내적주요약동학삼수 t1/2위（60.5±17.3）min、Cmax위（1299.1±201.0）ng·mL-1、AUC0-τ위（106.4±26.0）mg·min·L-1。간접반응억제모형의합적주요약효학삼수분별위Kin=（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）（이pH계）。결론뢰패랍서재건강지원자체내약동학부합일방실정맥적주모형，약효학과정부합간접반응억제결합모형적특정，용해모형계산득도적방정능유효건립기뢰패랍서혈약농도여효응간적대응관계。
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-1,and(106. 4±26. 0)mg·min·L-1, respectively.The corresponding PD parameters,Kin,Ke,IC50 and Imax 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 compartment 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.