Effects of Bile and Meal on the Gastrointestinal Absorption of 2-[3-(3, 5-Di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo [3, 4-b] pyridin-1-yl] ethyl Acetate, a New Non-steroidal Anti-inflammatory Agent

Publisher Website
Google Scholar
Abstract
The effects of bile and meal on the gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-1-yl]ethyl acetate (1), were investigated in rats and dogs. Compound 1 was lipophilic and soluble in bile, but extremely insoluble in water. The important role of bile in the dissolution step in the absorption process of 1 was confirmed on the in situ absorption study with rats. Oral absorption of 1 was insufficient and showed a marked individual difference in fasting dogs. When the same compound was administered after ingestion of a meal, the absorption increased with decreasing scatter. Three kinds of meals had different potencies to enhance the bioavailability of 1 in the order of lard > mashed potatoes > skimmed milk. The absorption behavior of 1 reflected small intestinal transit time and the stimulated bile output after ingestion of meal.