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In this study the effect of epomediol (1,3,3-trimethyl-2-oxabicyclo 2.2.2 ocatan-6,7-endo, endo-diol) (Clesidren) on rat hepatocyte bile acid transport was evaluated using [3H]-taurocholate as a probe, in order to clarify the mechanism of action of this drug. To this purpose, primary cultures were prepared with hepatocytes obtained from normal rats (Group I), and rats receiving a 4-day treatment with either epomediol (100 mg/kg) (Group II), or ethinyloestradiol (5 mg/kg) (Group III), or ethinyloestradiol plus epomediol (5 mg and 100 mg/kg respectively) (Group IV) or vehicle DMSO 50 microliters/kg) (Group V). All hepatocytes were isolated 10 days after the end of treatment. Hepatocyte [3H]-taurocholate uptake was evaluated in vitro after 48 hr of incubation in the presence or absence of epomediol. In both cases no difference was found when evaluating the uptake of hepatocytes from Group I, II and V. In the absence of epomediol [3H]-taurocholate uptake in hepatocytes from rats of Group IV was significantly higher than that observed in hepatocytes from rats of Group III. On the other hand, the presence of epomediol did not influence [3H]-taurocholate uptake in hepatocytes from rats of Group III, which remained significantly lower compared to that of control hepatocytes (Group V). The protective effect obtained when administering epomediol simultaneously with ethinyloestradiol (Group IV) was not due to its ability to compete with ethynyloestradiol for the binding to oestrogen receptors. Our results indicate that epomediol is able to restore a normal hepatocyte bile acid uptake when given in vivo simultaneously with ethinyloestradiol but does not influence bile acid transport in cultured hepatocytes. Further studies are required to better define the choleretic activity of this drug.