Comparison of effects of oral and intravenous famotidine on inhibition of nocturnal gastric acid secretion

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      In this double-blind, placebo-controlled, four-way crossover, randomized study, eight high-secretor (more than 5 meq per hour) volunteers received 20 mg of famotidine by mouth, 10 mg intravenously, and 20 mg intravenously at 9 P.M. Volume, acid content, and pH of continuous gastric aspirates were measured hourly from one to at least 12 hours after treatment. Plasma concentrations of famotidine were determined at specified intervals. All famotidine doses produced marked suppression of gastric secretion. The mean total output was 1,196.3, 526.8, 414.9, and 518.0 ml for placebo, the 10-mg intravenous famotidine dose, the 20-mg intravenous dose, and the 20-mg oral dose, respectively. The latter three values were significantly different from that of placebo at p <0.01. The mean total acid output was 105.3, 8.3, 2.3, and 6.2 meq, respectively, and the acid output for all three doses was significantly different from that of placebo at p <0.01. The onset of antisecretory effect was noted as early as one hour after dosing. The mean gastric aspirate pH values were 1.7, 5.5, 6.2, and 4.4 during the second hour after placebo, the 10-mg intravenous dose, the 20-mg intravenous dose, and the 20-mg oral dose, respectively, with the treatment pH values significantly different from the placebo pH value at p <0.01. Higher mean pH values were reached at seven, eight, and nine hours after the 20-mg intravenous dose than after the 10-mg intravenous dose (p <0.05). By the 12th hour after administration of the 10-mg intravenous dose, pH values had returned to baseline in all but one subject. After the 20-mg intravenous dose, a similar loss of effect occurred in one subject at 12 hours and in all subjects by 15 hours. Plasma concentrations of famotidine greater than 50 ng/ml were associated with an acid output inhibition of more than 80 percent, whereas high (more than 90 percent) as well as low (less than 50 percent) inhibition was observed at famotidine concentrations below 50 ng/ml.
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