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Effect of the hypolipidemic drug nafenopin (2-methyl-2-(p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy)propionic acid; TPIA; SU-13,437), on the hepatic disposition of foreign compounds in the rat.

W. G. Levine

Published 1974 in Drug Metabolism And Disposition

ABSTRACT

Rats fed for 2 days with the hypolipidemic drug, nafenopin {2-methyl-2-[ p -(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]propionic acid, TPIA, SU-13,437} show a marked increase in liver weight and a profound choleresis. In contrast, the blood disappearance, liver uptake, and biliary excretion of 7,12-dimethylbenzanthracene, succinylsulfathiazole, sulfobromophthalein, and phenol-3,6-dibromphthalein are severely depressed. These changes persist for several days after nafenopin is withdrawn. The effect may be specific for organic anions because the biliary excretion of procainamide ethobromide, an organic cation, is not suppressed. An increase in liver protein accompanies the increase in liver weight. Administration of ethionine, an inhibitor of protein synthesis, partially reverses the effect of nafenopin on bile flow and on the biliary excretion of foreign compounds. The possibility is considered that these effects may be related to the synthesis of protein associated with the liver uptake process as well as bile formation.

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