INFLUENCE OF SINGLE AND MULTIPLE DOSES OF ORAL RANITIDINE ON THE GASTRIC TRANSIT OF AN INDIGESTIBLE CAPSULE IN HUMANS

The effect of single and multiple doses of ranitidine on the gastric residence time of an indigestible pHsensitive 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 >_3 U) of the Heidelberg capsule was observed. Blood samples (n = 12) were collected 0 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-∞) were significantly increased, whereas Cmax, tmax, and t 1 2 remained unchanged after 7 days of ranitidine b.i.d. treatment. No ranitidine double-peak profile or linear pharmacokineticpharmacodynamic 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. © 1990.