Bioavailability and diuretic effect after administration of retarded capsules of bumetanide in human subjects

Retarded capsules containing 1 mg bumetanide (BN) were prepared and their in vivo absorption and diuretic effect after oral administration in human subjects were studied. For comparison, commercially available tablets of BN (rapid effect) were administered orally. The mean value of the area under the plasma concentration time curve (AUC) after administration of retarded capsules was about one half that of the tablets. The mean maximum plasma concentration (Cmax) and the mean maximum urinary excretion rate of BN after administration of retarded capsules were also about one half compared to those of the tablets. Cumulative urinary volumes for 24 h, however, were not significantly different between retarded capsules and tablets. Peak times for the urinary excretion rate of BN, urine flow rate and the Cmax after administration of retarded capsules were significantly delayed compared to those of tablets. Clockwise hysteresis relationships between the urine flow rate and plasma concentration or urinary excretion rate of BN were observed after administration of retarded capsules. From these studies, retarded capsules of BN possessed a mild diuresis and its diuretic effect was maintained for a few hours after administration.