Studies of the biliary excretion and metabolites of the antioxidant ethoxyquin, 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline in the rat.

1. Biliary excretion and metabolites of ethoxyquin, and gastro-intestinal absorption of ethoxyquin were studied in rat. 2. An average of 28 and 36% of the dose of 14C following intragastric administration of [14C]ethoxyquin was recovered in the bile of bile-duct cannulated rats in 12 and 24 h, respectively. 3. By g.l.c.-mass spectrometry, 75 to 85% of the 14C excreted in the 12 h bile was identified as unchanged ethoxyquin, and the following metabolites were isolated and identified: 8-hydroxy-ethoxyquin, hydroxylated 8-hydroxy-ethoxyquin, 6-ethoxy-2,2,4-trimethyl-8-quinolone, hydroxylated 6-ethoxy-2,2,4-trimethyl-8-quinolone, 6-ethoxy-2,4-dimethylquinoline and 2,2,4-trimethyl-6-quinolone. 4. Three groups of rats were used in the biliary excretion experiments, and the effect of standardization of experimental conditions was demonstrated. Infusion of sodium taurocholate following bile-duct cannulation did not affect the biliary excretion kinetics of ethoxyquin. 5. Only about 3% of the radioactivity administered was absorbed from the gastrointestinal tract via the lymphatic pathway in thoracic-duct connulated rats within 24 h. It was concluded that ethoxyquin was absorbed primarily by the portal route.