Abstract

The effects of hepatic disease on the pharmacokinetics of the histamine H2-receptor antagonist famotidine were studied in seven healthy volunteers and 20 patients with chronic liver disease. The acute effects of famotidine on hepatic hemodynamics were studied in six healthy volunteers and eight patients with chronic liver disease, and its long-term effects on peptic ulcer, portal blood flow, and hepatic function were studied in 34 patients with chronic liver disease and peptic ulcer. Famotidine clearance was reduced only in patients with decompensated cirrhosis, probably because of concomitant renal impairment. Infusion of 20 mg of famotidine did not reduce hepatic or portal blood flow in healthy subjects, nor did it reduce the gradient between wedged hepatic vein pressure and free hepatic vein pressure or hepatic and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg of famotidine twice daily for two months healed the peptic ulcers in 33 of 34 patients (97%) with chronic liver disease without altering portal blood flow and hepatic function. Even in patients with decompensated cirrhosis, famotidine did not change hepatic function. Thus, famotidine had no effect on hepatic hemodynamics or function in healthy subjects and patients with chronic liver disease. The drug was shown to be well tolerated and effective in the treatment of gastric and duodenal ulcer associated with chronic liver disease.