Combined Pharmacokinetics-pharmacodynamics Study of Rabeprazole in Inhibition of Gastric Acid Secretion / 医药导报

ABSTRACT

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.