Metabolic pathway of the diethylamide of trans-3-methyl-4-phenyl-3-butenoic acid, an hypolemic agent, in the rabbit

The metabolism of the hypolipemic agent 3-methyl-4-phenyl-3-butenoic acid diethylamide (I) after oral administration to rabbits has been qualitatively investigated. Four main metabolites were identified in the urine of animals deriving from three different metabolic processes: aromatic hydroxylation, lactonization and N-dealkylation. All metabolites occured in free forms, were pharmacologically inactive and the unchanged starting drug was never recovered. The metabolic pathway of compound I was also compared with that of the parent non-substituted amide, 3-methyl-4-phenyl-3-butenamide (II). The fate of the two structurally related drugs was similar, except for hydroxylation of the carbon in the alpha position to the amidic group, occuring in compound II but not in compound I.