Summary
Administration of nafenopin (SU-13-437) to male rats for two days leads to a doubling of bile production and a 50% increase in liver weight. These two effects have been shown not to be directly interrelated. A marked decrease in biliary bile salt concentration suggests that the bile salt independent flow is stimulated. The extra bile produced is probably of canalicular origin since bile to plasma concentration ratios of erythritol are unchanged. At least three polar metabolites of nafenopin have been observed in rat bile. Obervations in rats with partial biliary fistulas indicate that the drug and its metabolites undergo extensive enterohepatic circulation. Our studies support the view that much of the enhanced bile flow is associated with the presence of nafenopin and/or its metabolites within the hepatobiliary system. However, the response is too extensive to be explained merely by osmotic choleresis. Induced structural changes in the liver may also account for some of this effect.
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This research was supported by U.S. Public Health Service Grant CA 14231 from the National Cancer Institute
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Levine, W.G., Braunstein, I.R. & Meijer, D.K.F. Effect of nafenopin (SU-13,437) on liver function. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 221–234 (1975). https://doi.org/10.1007/BF00510552
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DOI: https://doi.org/10.1007/BF00510552