新規非ステロイド性抗炎症剤2-[3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-1-yl]ethyl Acetateの消化管吸収の改善

抄録

The effects of triglycerides 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 dogs. The enhancing abilities of the triglycerides on the absorption of 1 were demonstrated as in the order of trilinolein>triolein>tristearin>tripalmitin. Among the series of fatty acids and monoglycerides, namely, digestive products of triglycerides by pancreatic lipase, linoleic acid and monolinolein showed the most potent solubilizing activities of 1 in a solution of bile salt. The incorporation of 1 into mixed micelle formed by lipids and bile salts was presumed to play an important role in the accelerated absorption of 1 after ingestion of triglycerides. On the basis of these findings, an emulsion containing 1 was prepared with soybean oil. The emulsion exhibited a remarkable improvement of the absorption of 1 compared to a suspension of the drug in methylcellulose solution.