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.
ABSTRACT
Batifiban,a synthetic cyclic peptide,is a potent platelet glycoprotein GPⅡb/Ⅲa an-tagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects,and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55,110,or 220 μg/kg,or multiple doses of an bolus followed intravenous infusion for 24 h (180 μg/kg of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma lev-els of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner,consistent with its mechanism as a GP Ⅱb/Ⅲa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.