Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide

Abstract

After rapid intravenous injection of furosemide 40 mg (Fu), plasma levels were determined in 7 healthy volunteers, 8 patients with liver cirrhosis with ascites and 7 patients with end-stage renal disease (ESRD). The diuretic response was evaluated by measuring the urinary excretion of sodium and potassium and the urine volume. The mean elimination half life (t 1/2 beta) of Fu averaged 51 +/- 7.7 (+/- SD) min in healthy subjects, 52 +/- 7.7 min in cirrhosis and 200 +/- 57 min in ESRD. The non-renal clearance (Clnr) in healthy subjects (56 +/- 28 ml/min) corresponds to the total plasma clearance in functionally anephric patients (54 +/- 18 ml/min). In cirrhosis there was no significant change in the disposition parameters of Fu in comparison to the healthy volunteers, but there was a significant reduction in urine sodium and volume, whereas potassium excretion remained unchanged. Fu "excretion rate--response" curves showed diminished tubular sensitivity to Fu in cirrhosis.