Famotidine pharmacokinetics following oral and intravenous administration in patients with liver disease: results of a preliminary study.

The pharmacokinetics of famotidine were studied following single oral and intravenous 20-mg dose administration and after multiple oral 40-mg doses in 11 patients with alcohol-related cirrhosis of varying severity and in five healthy control subjects. No significant differences were observed, following single intravenous administration, in mean plasma famotidine half-lives or in mean plasma famotidine clearance values between the cirrhotic and control groups. Equally, values for mean maximum plasma famotidine concentrations and for mean times to peak plasma concentrations, estimated following single oral administration, were comparable between the groups. The mean (+/- s.d.) systemic availability of the drug, estimated from the areas under the curves, was 36 +/- 24% in the control subjects and 46 +/- 24% in the patients with cirrhosis. No significant increases were observed in trough plasma famotidine concentrations following multiple oral doses in the patients with cirrhosis and there was no evidence of drug accumulation. No significant changes were observed in psychometric performance in any of the patients or control subjects during the multiple-oral-dose study. Thus no significant changes occur in famotidine disposition in patients with cirrhosis even when their disease is decompensated. No reduction in drug dosage should therefore be necessary in these patients. Famotidine may produce less neurological side effects in patients with liver disease than the histamine H2-receptor antagonists used currently.