Pharmacokinetics of cimetidine in patients with liver disease.

Pharmacokinetics of cimetidine were studied after 200 mg i.v. doses in 7 patients with liver cirrhosis and in 10 healthy volunteers. Serial blood samples were obtained before and after drug administration over 12 hours. Cimetidine blood concentrations were determined by high pressure liquid chromatography (HPLC). The mean total body clearance in patients with cirrhosis (414.3 +/- 69.7 ml/min) was significantly less than that of subjects without liver dysfunction (501.1 +/- 37.9 ml/min) (p less than 0.01). However, the mean steady-state volume of distribution (1.34 +/- 0.41 l/kg vs 1.40 +/- 0.24 l/kg), volume of central compartment (0.51 +/- 0.11 l/kg vs. 0.45 +/- 0.05 l/kg), area volume of distribution (1.69 +/- 0.46 l/kg vs. 1.81 +/- 0.43 l/kg) and mean half-life (2.56 +/- 0.58 h vs. 2.68 +/- 0.43 h) did not demonstrate any significant changes. Renal clearance was significantly decreased from 389.5 +/- 41.9 ml/min in healthy subjects to 279.1 +/- 57.8 ml/min in cirrhotic patients (p less than 0.01). However, the mean extrarenal clearance was not changed in both groups. Modification of cimetidine dosage is therefore presumably not necessary in patients with compensated liver disease.