Effect of Small Intestinal Transit Time on 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 gastrointestinal absorption of 2-[3-(3, 5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3, 4-b]pyridin-1-yl]ethyl acetate (1), a new non-steroidal anti-inflammatory agent was investigated in dogs. A method using acetaminophen and salicylazosulfapyridine as the markers (double-marker method) was applied to trace the gastrointestinal transit of orally dosed 1. The mean absorption time of acetaminophen in plasma was used as an inidication of gastric emptying, and the first appearance time of sulfapyidine (a metabolite of salicylazosulfapyridine) in plasma was employed to detect the arrival of the marker to the colon. A remarkable inter-individual variation was observed in the absorption of 1. The extent of bioavailability was little affected by the gastric emptying time, but significantly influenced by the small intestinal transit time. Under a pretreatment with atropine, the transit time was prolonged to result in a significant enhancement of the bioavailability. Consequently, the absorption of 1 is confirmed to take place mainly in the small bowel.