One-day front-loading with four doses of rabeprazole followed by a standard twice-daily regimen provides sufficient acid inhibition in extensive metabolizers of CYP2C19.

Abstract

Four times daily dosing (qid) with a proton pump inhibitor can cause rapid increase in intragastric pH. We investigated the efficacy of the front-loading with rabeprazole 10mg qid on a subsequent regimen with rabeprazole 10mg twice daily (bid) for 7days in extensive metabolizers (EMs) of CYP2C19. Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10mg bid for 7days; (2) a front-loading regimen of rabeprazole (rabeprazole 10mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10mg qid for 7days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10mg bid regimen only. Twenty-four-hour intragastric pH-monitorings were performed on days 1, 4, and 7. Area under the intragastric pH-time curves (AUCs) from days 1 to 7 was calculated using 24-h median intragastric pHs on days 1, 4, and 7. Twenty-four-hour intragastric pHs in the front-loading group on days 1, 4, and 7 were 5.1, 4.9, and 5.1, respectively. The median AUC with front-loading in EMs (34.4, pH·day) was significantly higher than that in EMs with rabeprazole 10mg bid (30.74, p=0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10mg qid in EMs (37.2), rabeprazole 10mg bid in IMs (37.3), and PMs (39.4). The one-day front-loading regimen of rabeprazole 10mg qid provided sufficient acid inhibition for 7days, even in CYP2C19 EMs.