Diurnal secretory patterns and tolerance during individually titrated infusions of ranitidine

Abstract Background: Gastric acid secretion in humans shows chronobiological patterns that modify the efficacy of antisecretory agents. The ability of individually titrated ranitidine infusions to overcome circadian patterns of gastric acidity and tolerance during prolonged dosing was assessed. Methods: Eleven healthy subjects were randomized to receive ranitidine infusions of up to 600 mg/24 hours by a pH feedback-regulated pump before and after 9 days of oral dosing with ranitidine, 300 mg four times daily, beginning either in the evening or in the morning in a cross-over, third party-blinded and placebo-controlled study design. Results: Mean 24hour intravenous ranitidine doses given to attain the target pH of 4 were greater after 9 days of treatment with oral ranitidine than before in the morning and evening studies ( P P P 4 in the evening and morning fasting periods was 71% and 84%, respectively ( P P Conclusions: The reduced responsiveness to ranitidine in the evening and the tolerance to ranitidine with repeated dosing were not overcome by individually titrated, high intravenous doses of ranitidine.