Effect of suppository shape on the systemic availability of rectally administered insulin and sodium salicylate

There is increasing evidence to suggest that the systematic availability of drugs, particularly those that show significant first-pass metabolism, when administered rectally is dependent upon the site of absorption within the rectum (de Leede et al., 1983). The closer to the anus the drug resides the greater the systemic availability. This observation is usually explained in terms of the venous blood drainage within the rectum; the lower rectal area blood drains directly into the general circulation whereas the upper and middle rectal area blood drains directly into the portal system and undergoes first-pass hepatic metabolism. The role of the lymphatic system in drug dissemination and avoidance of first-pass metabolism from the rectum appears to have received little attention. Liversidge et al. (1985) have found that increasing surface area for absorption by increasing suppository size causes a decrease in systemic availability of rectally administered suppositories containing insulin and sodium salicylate. This observation