CHANGES IN BILIARY EXCRETORY MECHANISMS IN RATS WITH ETHINYLESTRADIOL-INDUCED CHOLESTASIS

Several excretory pathways for cholephilic compounds have been known. To examine the changes in excretory pathways in cholestasis induced by ethinyloestradiol, various bile acids, organic anions and organic cat ions were intravenously administered to ethinyloestradiol-treated rats and their biliary excretion was studied. Biliary excretion of tauroch olate was slightly delayed, but its excretory maximum was markedly dec reased. Biliary excretion of lithocholate-3-O-glucuronide, leukotriene C-4, sulphobromophthalein and pravastatin was markedly impaired to a similar extent. Biliary excretion of vinblastine, a P-glycoprotein sub strate, was increased, suggesting increased expression of P-glycoprote in. In contrast, biliary excretion of erythromycin, a cationic antibio tic, was markedly impaired. In conclusion, ethinyloestradiol treatment altered the biliary excretion of organic compounds, which may partly be related to changes of the canalicular transporters.