Study of the pharmacokinetics and intragastric pH of rabeprazole given as successive intravenous infusion to healthy Chinese volunteers.

OBJECTIVES

To investigate the pharmacokinetics and pharmacodynamics of rabeprazole (RPZ) given as successive intravenous infusion to healthy Chinese volunteers.

METHODS

A total of 63 subjects (33 males and 30 females) were recruited at four research centers and given a 5-day therapeutic course of RPZ (10, 20, or 40 mg) administered as single daily doses during a 30-min period. Plasma concentrations were monitored by sampling at very short intervals for the first 330, 360, or 420 min post-RPZ administration. Intragastric pH was recorded 24 h post-RPZ administration on day 1 and day 5.

RESULTS

After receiving a single and repeated doses of RPZ, the area under the plasma concentration-time curve (AUC(0-τ)) was 51.9 ± 22.1, 96.7 ± 27.6, and 188.4 ± 65.8 mg·min/L on day 1 and 59.3 ± 23.9, 106.7 ± 27.8, and 200.3 ± 79.0 mg·min/L on day 5 for the low-, middle-, and high-dose groups, respectively. The corresponding peak concentrations (C(max)) were 0.64 ± 0.11, 1.30 ± 0.26, and 2.6 ± 0.54 μg/mL on day 1 and 0.76 ± 0.15, 1.39 ± 0.25, and 2.91 ± 0.53 μg/mL on day 5, respectively. Although the mean AUC and C(max) values increased from a single dose to repeated doses in the three groups, the difference was not significant. The mean AUC((0, τ)) and C(max) ratios of repeated dose to single dose were 1.14, 1.10, and 1.06 on day 1 and 1.19, 1.07, and 1.12 on day 5 for the low-, middle-, and high-dose groups, respectively. After administration of a single dose, the 24-h pH value was significantly higher in the high-dose group than in the low-dose group. After repeated doses, significant increases in pH were observed in the low-, middle-, and high-dose groups; however, the between-group differences were not statistically significant.

CONCLUSIONS

There is a relationship between the pharmacokinetics and pharmacodynamics of RPZ, with the latter depending in part on the duration of administration, as evidenced by a higher AUC or C(max) and intragastric pH from repeated dosing.