Frusemide pharmacokinetics in patients with liver disease

Frusemide 80mg was administered intravenously to 10 patients with alcoholic liver disease (fatty liver and Laemnec's cirrhosis). Protein binding was correlated with serum albumin concentrations (r = 0.860, p < 0.001). The apparent volume of distribution ranged between 180 and 1206ml/kg body weight and correlated with the serum albumin concentration (r = 0.710, p < 0.05) and the fraction of unbound drug (r = 0.758, p < 0.05). This fraction was 1.9 +/- 0.2% in controls and 3.1 +/- 0.9% in patients with cirrhosis (p < 0.01). Plasma half-life of frusemide varied 7-fold, between 0.60 and 4.27h, and was prolonged substantially in some patients compared with values in normal subjects. There was a highly significant correlation between the apparent volume of distribution and plasma half-life of frusemide (r = 0.938, p < 0.001). Frusemide was eliminated via both renal and non-renal mechanisms in all but 2 patients, who had advanced cirrhosis and eliminated the drug almost exclusively though the kidneys. The apparent volume of distribution was increased proportionally more than the decrease in protein binding explaining in part why higher doses of frusemide are needed in patients with liver disease to obtain the same response as in healthy subjects.