Lack of effect of cimetidine on furosemide kinetics and dynamics in patients with hepatic cirrhosis.

Abstract

The influence of cimetidine on the natriuretic and diuretic responses to furosemide was studied in 10 patients with hepatic cirrhosis. After four days on a low sodium diet, the patients were given 40 mg of furosemide i.v. and from the sixth to the eleventh day they received 400 mg of cimetidine p.o. every 6 h and a second dose of furosemide with the last 6 h dose. Ten healthy subjects received the same dose of furosemide. Multiple blood and urine samples from both groups were analyzed for furosemide, sodium and creatinine. Furosemide kinetics were not affected in patients with hepatic cirrhosis but the effect was lower than in the controls: urinary excretion of sodium (0.47 +/- 0.07 vs 1.59 +/- 0.10 mmol/min, p < 0.05) and urine excretion (4.86 +/- 0.57 vs 9.16 +/- 0.85 ml/min, p < 0.05). The predicted maximal effect of furosemide (Emax) and the furosemide urinary rate of excretion needed to elicit 50% of Emax for the cirrhotic patients and the controls were 1.85 +/- 0.21 and 3.22 +/- 0.41 mmol/min (p < 0.05) and 137 +/- 15 and 99 +/- 12 micrograms/min (p < 0.05), respectively. The amounts of sodium filtered (FNa) and reabsorbed in response to the injection of furosemide were lower in the cirrhotic patients than in the controls, however, relative to the FNa, the cirrhotic patients reabsorbed more sodium than the controls. The administration of cimetidine did not affect the kinetics of furosemide nor its natriuretic or diuretic responses.(ABSTRACT TRUNCATED AT 250 WORDS)