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. 1983 The British Pharmacological Society