Effect of nafenopin (SU-13437) on liver function. Influence on the hepatic transport of phenolphthalein glucuronide and chlorothiazide.
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.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001693:Biological Transport, Active; D002740:Chlorothiazide / Q000378:metabolism*; D005260:Female; D005965:Glucuronates / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009255:Nafenopin / Q000494:pharmacology*; D009929:Organ Size; D010635:Phenolphthaleins / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D012737:Sex Factors
D005965:Glucuronates; D010635:Phenolphthaleins; D011422:Propionates; D009255:Nafenopin; D002740:Chlorothiazide