Absorption of glibenclamide from different sites of the gastro-intestinal tract.
In a study of eight volunteers and six patients, glibenclamide was placed at different sites of the gastro-intestinal tract under visual control. The dose was instilled once into the stomach and once into the duodenum of the eight volunteers in a randomized crossover design. The six patients underwent diagnostic colonoscopy, and the dose was placed into the ascending colon if pathological findings were not present. The area under the concentration-time curve, completed by extrapolation, and the mean residence time of the drug in the body were calculated. These pharmacokinetic characteristics were examined using a Jonckheere test for ordered alternatives and a Wilcoxon signed rank pair test. The means of the areas under the curve were 477 +/- 131 ng . h ml-1 for the stomach, 475 +/- 142 ng . h ml-1 for the duodenum and 486 +/- 301 ng . h ml-1 for the colon. The mean residence time changed from 2.67 +/- 0.35 h for the stomach to 2.42 +/- 0.48 h for the duodenum and 3.55 +/- 0.68 h for the colon. These results indicate that although glibenclamide is absorbed from all three sites of the gastro-intestinal tract to the same extent, the rates of absorption are different. It is discussed whether these findings really confirm the pH-partition hypothesis in drug absorption. Since glibenclamide--a weak acid--has a pK-value of about 6.5, these data seem to confirm the pH-partition hypothesis of drug absorption.
D000293:Adolescent; D000328:Adult; D004064:Digestive System / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male
D005905:Glyburide