The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

Abstract

1 Bumetanide (1 mg) was given orally and intravenously to a group of patients with chronic renal failure (n = 6) and to another group with cirrhosis of the liver (n = 8). 2 The pharmacokinetics, using a two-compartment model, and the pharmacodynamics of the drug in these patients were compared with those previously obtained for normal subjects. 3 In the renal group serum bumetanide concentrations were higher than for the normal subjects and the terminal half-lives were significantly prolonged (P less than 0.001). A decreased whole body clearance was attributable to a low renal clearance of drug, the non-renal clearance being significantly increased (P less than 0.01). 4 For the patients with liver disease, serum bumetanide concentrations were higher than for the renal group, and the terminal half-lives were significantly further prolonged (P less than 0.001). Both non-renal and renal clearances were significantly reduced (P less than 0.001). 5 Absorption rates were not significantly altered in either group and the values of F (bioavailability) were 0.82 and 0.95 for the patients with renal disease and hepatic disease, respectively. 6 A poor pharmacodynamic response and a reduced bumetanide excretion rate were observed for the patients with chronic renal failure, whereas with hepatic disease normal bumetanide excretion rates were observed with an impaired diuretic response.