Absorption, Distribution and Excretion of 3-(sulfamoyl[14C]methyl)-1,2-benziosoxazole (AD-810) in Rats, Dogs and Monkeys and of AD-810 in Men

Disposition of 3 - (sulfamoyl[14C]methyl) - 1,2-benzisoxazole ( [14C]AD-810) in rats, dogs and monkeys after oral administration in 20 mg/kg was studied. In preliminary human studies, healthy subjects ingested 200 mg of AD-810. [14C]AD-810 was found to be completely absorbed from digestive tracts in animals, since urinary and biliary excretion accounted for virtually total recovery of dosed radioactivity. Plasma levels reached maxima at several hours after administration in all species examined and decreased exponentially. In rats, tissue levels were virtually similar to plasma levels indicating rather even distribution in the body, and tissue radioactivity disappeared with the similar rate to plasma. Autoradiographic findings on the distribution were consistent with radiometric results. Radioactivity was evenly distributed in fetus in the pregnant rat with the similar level to maternal tissue levels. Like other sulfonamide derivatives, AD-810 was markedly taken up by erythrocytes in all species. [14C]AD-810 radioactivity was mostly excreted within 48 to 72 h after administration and its major route was urine in animals. In men, excretion of unchanged AD-810 and its metabolite in urine was found to be rather slow. No significant differences were found in absorption, distribution and excretion of radioactivity after 7 consecutive daily oral dosings of [14C]AD-810 in rats.