Pharmacokinetics of cimetidine in advanced cirrhosis.

Abstract

The effect of impaired liver function on the pharmacokinetics of cimetidine was studied in 8 patients with advanced cirrhosis given single doses of 100 mg i.v. and 400 mg p.o. on separate days. Compared to a control group of 10 healthy volunteers, the total renal and nonrenal clearance was significantly reduced in the cirrhotic patients; (total plasma clearance mean +/- SD) 356 +/- 181 vs 789 +/- 262 ml/min (p less than 0.01); renal clearance (Clr) 296 +/- 100 vs 588 +/- 181 ml/min (p less than 0.01) and nonrenal clearance ( Clnr ) 97 +/- 111 vs 205 +/- 89 ml/min (p less than 0.05). Compared to published results for age-matched ulcer patients, both total and nonrenal clearance were lower whereas renal clearance was within the reported normal range. A significant reduction in volume of distribution (Vd beta) was found, from 2.1 +/- 0.1 l/kg in controls to 1.0 +/- 0.4 l/kg, and in the patient group there was a significant correlation between Vd beta and total plasma clearance (r = 0.72, p less than 0.05). Volume of distribution in steady state (Vdss) did not differ from published results in age-matched controls. No significant change in half-life was found. Bioavailability, estimated by AUC-measurement, showed considerable patient variability (21-143%), with a mean of 70 +/- 39%. This was lower than in the controls. In contrast, measurement of urinary excretion showed higher bioavailability in the patients (66 +/- 23 vs 51 +/- 8%). No correlation was found between any of the kinetic parameters and the clinical and laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)