Biliary excretion of benzbromarone and its hydroxilated main metabolites in humans

Hepatic metabolism of the uricosuric drug benzbromarone results in the formation of two hydroxilated main metabolites M1 (1'-hydroxybenzbromarone) and M2 (6-hydroxybenzbromarone). As urinary excretion of benzbromarone and its metabolites is very low, we investigated biliary and plasma concentrations of the parent drug and the metabolites after oral administration of a single 100 mg dose of benzbromarone in 6 patients requiring diagnostic gastroduodenoscopy. Benzbromarone, M1 and M2 were detectable in bile samples 12 hours after drug application. No dehalogenated derivatives (bromobenzarone, benzarone) were present in the bile. 12h, 24h, and 36h plasma concentrations of the parent drug and the main metabolites varied substantially. Our data provide direct evidence of biliary excretion of benzbromarone and its hydroxilated main metabolites 1'-OH-bzbr (M1) and 6-OH-bzbr (M2) and demonstrate the lack of excretion of debrominated products.