Metabolites of 2-(3-Trifluoromethylphenyl)Tetrahydro-1,4-Oxazine (Cerm 1841) in Rats and Dogs

Abstract

1. In rats and dogs dosed with ¹⁴C-labelled 2-(3-trifluoromethylphenyl)tetrahydro-1,4-oxazine hydrochloride, the ¹⁴C was excreted mainly in the urine. The ¹⁴C eliminated in the faeces of dog was significantly higher than for rat.

2. Conjugated metabolites, mostly glucuronides, accounted for the greater part of the urinary radioactivity in both species.

3. Biotransformation products were predominantly acids in both species, followed by significant amounts of basic metabolites, with very little neutral substances.

4. The major urinary metabolite in rats was 3-trifluoromethylbenzoic acid and 3-trifluoromethylhippuric acid. In the dog it was 3-trifluoromethylmandelic acid in addition to the benzoic acid and its conjugate. The basic products identified in the urine of both species were unchanged drug and 1-amino-2-hydroxy-2-(3-trifluoromethylphenyl)ethane, with the first predominating.