Mar 1, 1976

Effect of nafenopin (SU-13437) on liver function. Influence on the hepatic transport of phenolphthalein glucuronide and chlorothiazide

Drug Metabolism and Disposition : the Biological Fate of Chemicals
T Uesugi, W G Levine

Abstract

In rats treated with the hypolipidemic drug, nafenopin (NP), for 2 days the biliary excretion of phenolphthalein glucuronide (PPG) was markedly decreased, while in contrast that of chlorothiazide (CTZ) was enhanced. This suggests the existence of independent hepatic transport mechanisms for these two anions. For both PPG and CTZ blood disappearance curves showed an initial, rapid phase followed by a second, slow phase. The rapid phase for both compounds is affected only slightly by pretreatment with NP. Therefore, it is inferred that suppression of biliary excretion was attributable mainly to impairment of the liver-to-bile transport process. The increased bile flow induced by NP treatment was previously shown to be related to the biliary excretion of NP and its metabolites. Inhibition of NP choleresis by PPG may involve competition for biliary transport of these compounds. The marked hepatomegaly and choleresis seen after NP pretreatment was more evident in male rats than in females.

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Mentioned in this Paper

SU-13,437
Chlorothiazide
Molecular Transport
Hepatic
Glucuronic Acids
Visual Suppression
Body Excretions
Excretory Function
Metabolic Inhibition
Metabolic Suppression

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