1984 年 104 巻 11 号 p. 1181-1190
The distribution, metabolism and excretion of 14C-azosemide, a new loop diuretic, were studied in rats after bolus intravenous administration and compared with those of other diuretics such as furosemide or bumetanide. The plasma levels of azosemide declined biexponentially, and the half lives estimated were 3.4 min (t1/2α) and 32 min (t1/2β). The whole-body autoradiograms showed that the radioactivity distributed with higher concentrations in the kidney and liver than in the whole blood. In pregnant rats, the distribution profiles were similar to those of male rats. And the radioactivity distributed with lower concentrations in the placenta, uterus and ovarium than in the whole blood, scarcely in the fetus and amniotic fluid. The urinary and fecal excretion of radioactivity were 40 and 58% of the dose, respectively. The biliary excretion was 67% of the dose, and a part of biliary excreta was reabsorbed. The urinary and biliary metabolites were separated on a thin-layer chromatography, and the structures were determined by mass spectra. The total recovery of unchanged drug in 24 h-urine and -bile was only 15% of the dose. And major metabolites were 4-amino-2-chloro-5-(1H-tetrazol-5-yl) benzenesulfonamide and azosemide glucuronide, along with several unidentified minor metabolites. As a result, azosemide was eliminated as rapidly as other diuretics in rats. The metabolic pathway was similar to that of furosemide having a similar chemical structure, but the excretion profile was similar to that of bumetanide with considerably different structure.