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
| Autor: | Hideo Kaneko, Yoshitaka Tomigahara, Mihoko Onogi, Iwao Nakatsuka, Setsuo Yamane |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Radioisotope Dilution Technique Stereochemistry Metabolite Propynyl Administration Oral Phthalimides Kidney Rats Sprague-Dawley Hydroxylation Excretion chemistry.chemical_compound Oral administration Oxazines Animals Moiety Carbon Radioisotopes Chromatography Herbicides General Chemistry Metabolism Benzoxazines Rats Metabolic pathway Liver chemistry Female General Agricultural and Biological Sciences Oxidation-Reduction |
| Zdroj: | Journal of Agricultural and Food Chemistry. 47:2429-2438 |
| ISSN: | 1520-5118 0021-8561 |
| DOI: | 10.1021/jf981007r |
| Popis: | On single oral administration of (14)C-S-53482 [7-fluoro-6-(3,4,5, 6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3( 4H)-one, Flumioxazin] labeled at the 1- and 2-positions of tetrahydrophthaloyl group to rats at 1 (low dose) or 100 (high dose) mg/kg, the radiocarbon was almost completely eliminated within 7 days after administration in both groups with generally very low residual (14)C tissue levels. The predominant excretion route was via 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-tetrahydrophthalimide moiety and hydroxylation of the cyclohexene or cyclohexane ring. One urinary and four fecal metabolites were identified using chromatographic techniques and spectroanalyses (NMR and MS). Three of five identified 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 identified in this study, the metabolic pathways of S-53482 in rats are proposed. To specify tissues forming reduced metabolites, an in vitro study was conducted. Reduction was found to take place in red blood cells. |
| Databáze: | OpenAIRE |
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