BACKGROUND: 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 10 mg qid on a subsequent regimen with rabeprazole 10 mg twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19. METHODS: Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10 mg 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. RESULTS: 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 10 mg bid (30.74, p = 0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid in IMs (37.3), and PMs (39.4). CONCLUSIONS: The one-day front-loading regimen of rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in CYP2C19 EMs.
RCT Entities:
BACKGROUND: 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 10 mg qid on a subsequent regimen with rabeprazole 10 mg twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19. METHODS: Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10 mg 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. RESULTS: 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 10 mg bid (30.74, p = 0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid in IMs (37.3), and PMs (39.4). CONCLUSIONS: The one-day front-loading regimen of rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in CYP2C19 EMs.
Authors: N Shirai; T Furuta; Y Moriyama; H Okochi; K Kobayashi; M Takashima; F Xiao; K Kosuge; K Nakagawa; H Hanai; K Chiba; K Ohashi; T Ishizaki Journal: Aliment Pharmacol Ther Date: 2001-12 Impact factor: 8.171
Authors: T Furuta; K Ohashi; K Kosuge; X J Zhao; M Takashima; M Kimura; M Nishimoto; H Hanai; E Kaneko; T Ishizaki Journal: Clin Pharmacol Ther Date: 1999-05 Impact factor: 6.875