Oxmetidine (SK&F 92994): Pharmacokinetic study in patients with liver cirrhosis

The pharmacokinetics of oxmetidine (SK&F 92994) were investigated in nine cirrhotic patients and compared with ten control subjects with gastroduodenal ulcers, but without any symptoms of hepatic pathology. On two separate occasions each patient received 200 mg oxmetidine as a single oral dose and 100 mg as a single intravenous dose. In the cirrhotics, the bioavailability of the oral dose and the plasma elimination half-life after both oral and intravenous administration were significantly higher than in the controls. Moreover, a positive correlation was found between the plasma elimination half-lives and the biochemical parameters of cholestasis. Such findings indicate that in severe liver disease and in cholestasis the accumulation of oxmetidine in the circulation may limit the use of this drug.