Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482, Flumioxazin) in the rat: II. Identification of reduced metabolites

On single oral administration of C-14-S-53482 [7-fluoro-6-(3,4,5,6-tetrahyd rophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3(4H)-one, Flumioxazin] lab eled at the 1- and 2-positions of tetrahydrophthaloyl group to rats at 1 (l ow dose) or 100 (high dose) mg/kg, the radiocarbon was almost completely el iminated within 7 days after administration in both groups with generally v ery low residual C-14 tissue levels; The predominant excretion route was vi a the feces. The major fecal and urinary metabolites involved reduction or sulfonic acid addition reactions at the 1,2-double bond of the 3,4,5,6-tetr ahydrophthalimide moiety and hydroxylation of the cyclohexene or cyclohexan e ring. One urinary and four fecal metabolites were identified using chroma tographic techniques and spectroanalyses (NMR and MS). Three of five identi fied metabolites were unique forms, reduced at the 1,2-double bond of the 3 ,4,5,6-tetrahydrophthalimide moiety. On the basis of the metabolites identi fied in this study, the metabolic pathways of S-53482 in rats are proposed. To specify tissues forming reduced metabolites, an in vitro study was cond ucted. Reduction was found to take place in red blood cells.