Controlled entry of orally administereddrugs: physiological considerations

AbstractPhysiological considerations bearing on the controlle entry into the systemic circulation of orally administered drugs in healthy man are reviewed. The most desirable site for drug absorption is the sterile portion of the small intestine, so that the time “window” available for absorption is not greater than the minimum small intestinal residence time in this segment. This appears to vary widely between individuals. Methodology for sampling intestinal content and for defining the fraction absorbed and the physical state of an administered drug are summarized. Small intestinal transit and gastric emptying rates are now estimated in man by imaging techniques using Tc99m labeled sulfur colloids. Small intestinal transit may also be estimated non-invasively by measuring breath H2 after administration of a meal containing a non-absorbable disaccharide such as lactulose, but the validity of such a method is uncertain because of the acceleration of intestinal transit by lactulose. The major determinants ...