Pharmacokinetics and pharmacodynamics of injectable dex-rabrazole for healthy people

Objective To study the pharmacokinetic and pharmacodynamic characteristics of dex-rabeprazole for injection at different doses in healthy subjects and to evaluate its safety. Methods A randomized, open, positive drug control trial design was adopted in this study. Forty healthy subjects were divided into 4 groups (n=10), and underwent intravenous infusion of dex-rabeprazole at 10 mg/qd, 10 mg/q12h, 20 mg/q12h and rabeprazole sodium 20 mg/q12h, respectively. The intragastric pH value was monitored for 24 h on the first and fifth days after administration. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to determine the blood dex-rabeprazole concentration. WinNonlin7.0 and SAS9.4 software was conducted to analyze and process the obtained data. Results The pharmacokinetic parameters on the first and fifth days of the subjects after intravenous infusion of dex-rabeprazole 20 mg/q12h were Cmax 1.70±0.46 and 1.74±0.49 μg·mL-1 and AUC0-t 2.19±0.59 and 2.21±0.51 μg·mL-1 (significantly higher than the other 3 groups); Tmax 0.51±0.03 and 0.50±0.00 h (similar to the other 3 groups); and T1/2 1.93±0.73 and 1.82±0.67 (higher than the 10 mg/qd and 10 mg/q12h groups and slightly lower than the rabeprazole sodium 20 mg/q12h). The percentage of time with intragastric pH value >4.0 after the first and fifth days of medication was (82.27±10.13)% and (93.16±5.84)% in the dex-rabeprazole 20 mg/q12h group, statistically higher than those in the other 3 groups. The percentage was also higher in the rabeprazole sodium 20 mg/q12h group than the 10 mg/qd and 10 mg/q12h groups. One case from the dex-rabeprazole 20 mg/q12h group experienced mild adverse event (pain in the back of the thigh) and relieved after that spontaneously. No serious adverse events were observed in each group. Conclusion Injectable dex-rabeprazole shows good pharmacokinetic and pharmacodynamics effects, and has sound safety to healthy subjects.