[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].
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 bio-availability of 1 in the order of lard greater than mashed potatoes greater than skimmed milk. The absorption behavior of 1 reflected small intestinal transit time and the stimulated bile output after ingestion of meal.
Mizuta
H
H
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Kawazoe
Y
Y
Haga
K
K
Ogawa
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001646:Bile / Q000502:physiology*; D001682:Biological Availability; D004285:Dogs; D005260:Female; D005502:Food; D007408:Intestinal Absorption; D008297:Male; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D011725:Pyridines; C066887:2-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo(3,4-b)pyridin-1-yl)ethyl acetate