The inhibition of drug metabolism by cimetidine in patients with liver cirrhosis.

The effect of cimetidine treatment, 1 g daily over 6 days, on the disposition of theophylline was studied in nine patients with liver cirrhosis and in nine patients without liver disease. Plasma elimination half-life tended to increase from 14.6 +/- 8.2 h to 24.3 +/- 14.1 h in the cirrhotic patients (P greater than 0.05) and from 8.3 +/- 4.2 h to 10.3 +/- 4.1 h in the control patients (P less than 0.05). Total plasma clearance decreased from 0.50 +/- 0.23 ml/kg/min to 0.41 +/- 0.21 ml/kg/min (P less than 0.05) in the cirrhotics and from 0.77 +/- 0.34 ml/kg/min to 0.58 +/- 0.18 ml/kg/min (P less than 0.05) in the controls. Pretreatment clearance values were also significantly reduced in the cirrhosis group. No change was observed in the volume of distribution of theophylline. The degree of inhibition of theophylline metabolism did not depend on whether the patients were smokers, or whether they had low pretreatment clearance values. In liver cirrhosis, inhibition of drug metabolism by cimetidine varies widely and is unpredictable in the individual patient.