[Improvement of 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].
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 greater than triolein greater than tristearin greater than 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.
Mizuta
H
H
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Samemoto
H
H
Ogawa
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001647:Bile Acids and Salts; D004285:Dogs; D004655:Emulsions; D007408:Intestinal Absorption / Q000187:drug effects*; D008055:Lipids; D008297:Male; D008823:Micelles; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics*; D012995:Solubility; D014280:Triglycerides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001647:Bile Acids and Salts; D004655:Emulsions; D008055:Lipids; D008823:Micelles; D011720:Pyrazoles; D011725:Pyridines; D014280:Triglycerides; C066887:2-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo(3,4-b)pyridin-1-yl)ethyl acetate