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Effect of nafenopin (SU-13, 437) on liver function

Influence on the hepatic transport of organic anions

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Summary

Rats treated with the hypolipidemic agent, nafenopin (SU-13, 437) exhibit a higher plasma retention and a markedly reduced biliary excretion of organic anions, such as sulfobromophthalein (BSP) and its dibromo analog (DBSP), indocyaninegreen (ICG), succinylsulfathiazole (SST) and polar metabolites of bilirubin and the carcinogens 7, 12-dimethylbenzanthracene (DMBA) and 3,4-benz-pyrene (BP), despite an increase in liver mass and a profound choleresis. However, taurocholate is not affected in this manner, which supports the idea of a transport mechanism for taurocholate that differs from that of other organic anions. A pharmacokinetic study was made for DBSP in vivo. After nafenopin treatment, primary hepatic uptake (k12) and transport from liver into bile (k23) are reduced in vivo. Infusion studies indicate that biliary transport maximum (Tm) for DBSP is also decreased although the calculated hepatic storage (S) is only moderately affected. In the isolated perfused liver, hepatic clearance and biliary excretion of BSP are reduced by two-thirds. The time course of anion tranport inhibition and the hepato-biliary disposition of 14C-nafenopin suggest a direct effect of the drug. The extra liver mass induced by nafenopin appears to be hypo- or nonfunctional with respect to hepatic transport of organic anions.

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Author notes

  1. Dirk K. F. Meijer

    Present address: Department of Pharmacology, State University of Groningen, Bloemsingel 1, Groningen, The Netherlands

Authors and Affiliations

  1. Department of Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York

    Dirk K. F. Meijer, John Bognacki & Walter G. Levine

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  1. Dirk K. F. Meijer
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  2. John Bognacki
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  3. Walter G. Levine
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Additional information

Supported by U.S. Public Health Service Grant CA 14231 from the National Cancer Institute.

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Meijer, D.K.F., Bognacki, J. & Levine, W.G. Effect of nafenopin (SU-13, 437) on liver function. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 235–250 (1975). https://doi.org/10.1007/BF00510553

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  • DOI: https://doi.org/10.1007/BF00510553

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