Pharmacodynamics of Famotidine in Humans

The physiologic role of histamine (H2) receptors and their involvement in pharmacologic responses have not been completely defined. To date, H2-receptor-specific pharmacologic actions of H2-receptor inhibitors in humans are primarily associated with effects on gastric acid secretion. Famotidine is a new potent competitive inhibitor of H2 receptors. During its development, in addition to studies defining its gastric acid antisecretory profile, famotidine was also examined for potential effects on other functions of the gastrointestinal tract and on other systems. Famotidine inhibits basal and stimulated gastric acid secretion in a dose-dependent manner after oral administration of 5 to 40 mg. Maximal effect is achieved by the 40-mg dose, with peak activity reached one to three hours after dosing and a duration of action lasting 10 to 12 hours. Gastric emptying times and exocrine pancreatic function are not affected after famotidine (40 mg twice daily) treatment. Blood pressure, heart rate, and electrocardiographic patterns remain unchanged after oral or intravenous administration of famotidine in doses up to 40 mg and 20 mg, respectively. Serum prolactin levels do not rise after intravenous administration of 20 mg of famotidine. The levels of prolactin, testosterone, dehydroepiandrosterone, follicle-stimulating hormone, luteinizing hormone, and other circulating hormones remain unchanged during four weeks of treatment with famotidine 40 mg daily. Renal inulin and creatinine clearances show no change after intravenous administration of 10 mg of famotidine, and tubular excretion of procainamide and its major metabolite is unchanged after administration of 40 mg of famotidine. No significant effects are found on the biologic disposition of theophylline, warfarin, and other compounds metabolized by the liver cytochrome P450 enzyme system when they are given concomitantly with famotidine.