Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were compared in vitro dissolution profile and in vivo absorption studies. The dissolution of F from retarded capsules was extremely restricted in the first fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F from tablets and retarded capsules in the second fluid of JP XII disintegration test were both complete. Metabolite specific assay of F showed F, conjugation of F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or plasma. The mean cumulative urinary excretion of F following administration of the tablets during 24 h was twice that of retarded capsules. The mean area under the plasma concentration-time curve (AUC) of F following administration of tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume during 24 h, however, was not significantly different between the two dosage forms. Clockwise hysteresis relationships between the diuretic response and the urinary excretion rate of F was observed after administration of retarded capsules. A straight relation between logarithm of the diuresis and logarithm of the urinary excretion of F was observed after maximum excretion rate of F following administration of both dosage forms.

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.

No abstract