Absorption Characteristics of U-63,287 as Evaluated by In Situ Rat Gut Perfusion
Bangs, Mark E.
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Bioavailability refers to the overall rate and extent to which the active form of a drug enters the general circulation after oral administration. Bioavailability has been found to depend on many factors, among them the rate of dissolution of the dosage form, the permeability of the intestinal mucosa to the drug, the rate of gastric emptying, intestinal motility, and interactions between the drug and intestinal contents. In characterizing the absorption of a drug, experiments are done to determine the region of optimum absorption within the gastrointestinal tract, the mechanism(s) and kinetics of absorption, and other critical physiochemical and biological factors influencing absorption. This project characterizes the absorption in the rat's intestines of U-63,287, an oral antidiabetic drug. The method used to study U-63,287's absorption is a modification I of an in situ intestinal perfusion technique developed by Schanker et al.(l958). The studies performed during this project include a comparison of the relative absorption rates of U-63,287 in three different intestinal segments, a quantitative analysis of absorption of U-63,287 from the duodenum into the mesenteric lymph, a study of the relationship between perfusate residence time and intestinal absorption, and a study of U-63,287 absorption at different pHs.