PHARMACODYNAMICS AND DOSE-RESPONSE RELATIONSHIP OF FAMOTIDINE - A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED TRIAL

The dose-response relationship of oral famotidine at doses up to 10 mg was evaluated lo healthy male subjects to assess the extent and durat ion of inhibition of meal-stimulated intragastric acid secretion. Each subject received single oral administrations of famotidine 0.5, 2.5, 5.0, and 10.0 mg and placebo in a double-blind, randomized, cross-over fashion. Intragastric pH was measured every 4 seconds for 24 hours, a nd expressed as the mean pH for each 10-minute interval. Standard high -protein meals were provided 1 hour before each dose of study drug and at 3 and 9 hours postdose. The mean intragastric pH was significantly higher after famotidine doses 2.5, 5.0, and 10.0 mg than after placeb o at times 2.5 to 3.0, 1.8 to 3.2, and 1. 7 to 4.2 hours postdose, res pectively. There were no significant differences in mean pH seen betwe en famotidine 0.5 mg versus placebo. The range of the pH means between 1.7 and 3.2 hours postdose was placebo (1.0 to 1.3). famotidine 0.5 m g (1.1 to 1.4), 2.5 mg (1.4 to 1.7), 5.0 mg (1.7 to 2.1), and 10.0 mg (2.0 to 2.3). There was a statistically significant linear dose-respon se relationship between famotidine dose and intragastric pH between 1. 7 and 3.8 hours and from 6.3 to 8.7 hours after ingestion.