Effect of nafenopin (SU-13,437) on liver functions. Hepatic uptake and biliary excretion of ouabain in the rat.

Pretreatment of rats for 2 days with the hypolipidemic drug, nafenopin, 0.5 g/kg, results in an increase in liver weight and bile flow. Despite these changes, hepatic transport of ouabain is reduced. This was demonstrated in the isolated perfused liver as well as in vivo. Although net uptake into liver is diminished in treated rats, the initial rapid phase of the plasma disappearance curve is unaffected. This suggests that the primary uptake process is unaffected by nafenopin or is altered in a manner that is not reflected in this phase of plasma disappearance. Alternatively, nafenopin may increase ouabain efflux from liver to plasma. Biliary excretion of ouabain is markedly suppressed after nafenopin pretreatment and higher liver levels of ouabain were encountered after the first 20 min in treated animals. The inference is drawn that liver to bile transport of ouabain is also suppressed by nafenopin pretreatment.