BIOAVAILABILITY AND DIURETIC EFFECT OF FUROSEMIDE FOLLOWING ADMINISTRATION OF TABLETS AND RETARDED CAPSULES TO HUMAN-SUBJECTS

Two kinds of dosage forms (tablets and retarded capsules) of furosemid e (F) mere compared in vitro dissolution profile and in vivo absorptio n studies. The dissolution of F from retarded capsules was extremely r estricted 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 glucuro nic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or pl asma. The mean cumulative urinary excretion of F following administrat ion of the tablets during 24 h was twice that of retarded capsules. Th e mean area under the plasma concentration-time curve (AUG) of F follo wing administration of tablets was 1.5 times that of retarded capsules , The mean cumulative urine volume during 24 h, however, was not signi ficantly 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 st raight relation between logarithm of the diuresis and logarithm of the urinary excretion of F mas observed after maximum excretion rate of F following administration of both dosage forms.