Abstract

Halofenata was repidaly Hydrolysed after oral administration to rats and dongs to the correponding free acid (pCholorophenyl)(m-trifluoromethylphenoxy)acetic acid (HFA). HFA was extensively bound to plasma protein. Administration of ¹⁴C-labeled halofenate to rats resulted in distribution of radioactivity to various tissues but highest concenration of label were found in plasma. A large fraction of the dose was excreted flllowed by extensive reabsorption of the biliary radioactivity. Biliary excretion in the dog was less extensive. The dose was excreted equally in rat urine and feces but predominantly in dog feces. A major metabolite in urine of both species was hydroxylated in the trifluoromethyiphenoxy ring. Chronic administration of halofenate to dogs resulted in a slow increase in plasma levels. Administration of halofenate-¹⁴C to the rhesus monkey and man gave similar excretion patterns, 46% to 56% the dose being excreted in urine and 25 to 27% in feces in five to six days. Halofenate was evidently rapidly converted on absorption to the corresponding acid, HFA, since only the latter was found in plasma of all species after administration of halofenate. The plasma T_1/3, was approximately 16 hours in the monkey and 24 hours in man, with a slower phase (post-24 hours) with T_1/3, of approximately 48 hours. About 70% of the urinary radioactivity in both species was represented by HFA with the remainder present as HFA-glucuronide.