Circadian differences in pharmacological blockade of meal-stimulated gastric acid secretion

The effects of identical morning (08.05 hours) and evening (20.05 hours) meals on intragastric pH were compared in 12 healthy volunteers receiving gastric antisecretory medication. Dosing included continuous intravenous infusion ranitidine (50 mg bolus followed by 12.5 mg/h) or a matching placebo which were randomly administered prior to and following 7 days of treatment with oral omeprazole (40 mg mane). Intragastric pH was monitored continuously using a tethered indwelling pH probe. Subjects were divided into groups, one of which began the pH monitoring session in the morning, the other in the evening. The median 24-h intragastric pH was significantly increased by all active dosing regimens (P less than 0.05). Combined omeprazole and ranitidine produced the highest median pH, 5.92. However, a breakthrough drop in intragastric pH occurred during the evening after all active dosing. Intragastric pH fell prior to and after consumption of the evening meal with median pH values less than 4 during all sessions. The evening meal led to significantly lower intragastric pH compared to the morning meal for omeprazole and the combined omeprazole and ranitidine dosing periods (P less than 0.05). There was no difference between morning and evening pH during the placebo or ranitidine periods. Ranitidine and omeprazole, either alone or in combination, were unable to prevent the meal-stimulated decline in intragastric pH during the evening time period.