The metabolic fate of 11-bromo[15-3H]vincamine in man

During 5 days following a single oral dose of 3H-11-bromovincamine (40 mg) to two human subjects, means of 55% and 27% of the 3H dose were excreted in the urine and faeces respectively, mainly within 24 and 48 h. Mean plasma concentrations of 3H reached a peak (1900 ng equiv./ml) at 1 h after dosing and declined biphasically with half-lives of 5 h and 11 h which were similar to half-lives for urinary excretion of 3H. Parent drug and 11-bromovincaminic acid were the major dose-related components in plasma at 1.5 and 3 h. Mean plasma concentrations of 11-bromovincamine reached a peak (620 ng/ml) at 0.75 h and declined biphasically with half-lives of about 1 h and 5 h. The major urinary metabolite was 11-bromovincaminic acid (31% dose). Also present in urine were 11-bromovincamine (3%), 11-bromoapovincamine (1%) and 2 unknown metabolites (9% and 6%). Similar metabolites were detected in faecal extracts. If inadequately stored in biological samples, 11-bromovincamine could be hydrolysed to 11-bromovincaminic acid and be epimerised to 11-bromo-epivincamine.