Probenecid-induced effects on bile flow and biliary excretion of 3H-ouabain.

Probenecid-induced effects on bile flow and biliary excretion of exogenous compounds, e.g. 3H-ouabain were investigated on bile-fistula rats. Clearance measurements of 14C-mannitol under incresed doses of probenecid gave evidence that the drug acts at the canalicular site only. Biliary excretion of radioactivity after 14C-probenecid administration was found to be saturated at a dosage of 100 mg X kg-1. Probenecid exerts its choleretic effect by osmotic activity in a "bile acid-like" manner. This is confirmed by a close positive correlation between the excretion of radioactivity after treatment with 14C-probenecid and bile flow. The effects of probenecid on the biliary excretion of exogenous compounds, e.g. ouabain, imply beside choleresis also inhibitory effects on transport systems. As a result of both effects the biliary excretion of ouabain remains unchanged within a within a wide range of probenecid doses.