Metabolism of ethyl apovincaminate in the rat

Ethyl apovincaminate (RGH-4405, Cavinton) is well metabolized in rat, and only a small fraction of the original compound is excreted in urine. The main urinary metabolite is apovincaminic acid, hydrolytical product of Cavinton produced partly by plasma esterases. In plasma only the original compound and free acid are detectable. Several other metabolites have been isolated from bile and characterized by mass spectrometry. Cavinton is hydroxylated at the indole moiety and forms conjugates (possibly glucuronide and sulfate). The glycine derivative of apovincaminic acid containing two hydroxygroups has been detected in significant amounts, analysed by mass spectrometry. Among minor metabolites vincaminic acid ethyl ester has been found. More than 80% of total urinary and 50% of total biliary metabolites have been identified by radiochromatography, mass and IR spectroscopy.