Influence of single and multiple doses of oral ranitidine on the gastric transit of an indigestible capsule in humans

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Abstract
The effect of single and multiple doses of ranitidine on the gastric residence time of an indigestible pH-sensitive radiotelemetric device, the Heidelberg capsule, was evaluated in 12 healthy men (mean age, 29 .+-. 8 years) in a placebo-controlled, randomized, crossover study. Each subject received 150 mg ranitidine or placebo orally 2 hours before administration of the Heidelberg capsule. A 500 kcal standardized breakfast was served 1/2 hour before the capsule was administered. Gastric pH was monitored at 15-minute intervals, until pyloric passage (pH increase .gtoreq.3 U) of the Heidelberg capsule was observed. Blood samples (n = 12) were collected o to 8 hours after administration of drug or placebo. The subjects continued to receive ranitidine or placebo b.i.d. for 7 days and returned on day 8 for a similar evaluation. After a 1-week washout period, the subjects received the alternative treatment. The mean (.+-.SD) gastric residence time of the Heidelberg capsule was significantly decreased after both single and multiple doses of ranitidine compared to placebo (3.1 .+-. 0.9 versus 3.8 .+-. 1.1 hours, p < 0.02; and 2.9 .+-. 0.74 versus 3.9 .+-. 0.9 hours, p < 0.005, n = 9). Gastric residence time was not determined in three subjects who showed unusually slow gastrointestinal motility after both placebo and ranitidine. Mean AUC(0-8 hr) and AUC(0-.infin.) were significantly increased, whereas Cmax, tmax, and t1/2 remained unchanged after 7 days of ranitidine b.i.d. treatment. No ranitidine double-peak profile or linear pharmacolineticpharmacodynamic relationship was identified. In conclusion, the findings of this study indicate that ranitidine may accelerate the gastric transit of indigestible solid dosage formulations by approximately 1 hour.