Clinical pharmacokinetics of famotidine

Abstract

Famotidine is a potent histamine H2-receptor antagonist widely used in the treatment and prevention of peptic ulcer disease. After intravenous administration the plasma famotidine concentration-time profile exhibits a biexponential decay, with a distribution half-life of about 0.18 to 0.5h and an elimination half-life of about 2 to 4h. The volume of distribution of the drug at steady-state ranges from 1.0 to 1.3 L/kg; plasma protein binding is low (15 to 22%). Famotidine is 70% eliminated unchanged into urine after intravenous administration. The total body and renal clearances of famotidine correlate significantly with creatinine clearance. Because its renal clearance (15 L/h) far exceeds the glomerular filtration rate, famotidine is considered to be eliminated not only via glomerular filtration but also via renal tubular secretion. Since its clearance is reduced in patients with renal insufficiency and in elderly patients, the maintenance dosage should be reduced in these patient groups. Removal of famotidine by any of the currently employed blood purification procedures (haemodialysis, peritoneal dialysis and haemofiltration) does not occur to a clinically significant degree. Liver cirrhosis does not appear to affect the disposition of famotidine unless severe renal insufficiency coexists. After oral administration, peak plasma concentrations are attained within 2 to 4h; the oral bioavailability ranges from 40 to 50%, due mainly to incomplete absorption. The oral absorption of the drug is dose-independent within a range of 5 to 40 mg. There are 3 formulations available (tablet, capsule and suspension), which appear to be bioequivalent. Coadministration of potent antacids reduces the oral absorption of famotidine by 20 to 30%. On a weight-to-weight basis, the antisecretory effect of famotidine is about 20 and 7.5 times more potent than those of cimetidine and ranitidine, respectively. Plasma famotidine concentrations correlate with its antisecretory effect: values of about 13 and 20 micrograms/L produce a 50% reduction in the gastrin-stimulated gastric acid secretion and a fasting intragastric pH of greater than 4, respectively. Available data suggest that famotidine interacts neither with the hepatic oxidative drug metabolism nor with the tubular secretion of other commonly used therapeutic agents. However, further studies are required to evaluate a full spectrum of its drug interaction potential.