**15. Rectal absorption**

The rectum is the final part of the intestinal tract and about 4-5 inches long. It is the part of the gastrointestinal tract that extends from the colon in the lower left part of the abdomen to the anus. Its temperature is the same as the body temperature, constant at 37 oC. For insulin to be administered rectally, it needs to pass through the rectal epithelia, lamina propria and muscularis mucosa. The rectum has a rich vasculature making it a good site for drug administration.

For maximum absorption, insulin suppositories should not be inserted too high into the rectum since the superior rectal vein takes blood straight to the liver, where first pass effect is taking place. Inserting insulin to the lower part of the rectum will result in insulin permeation to the inferior or middle rectal veins which drain into the inferior vena cava bypassing the liver and avoiding first pass metabolism. However, reaching the higher part of the colon is not feasible thus rendering insulin rectal delivery ineffective. Enhancing insulin rectal absorption can be achieved using bile salts (Sayani & Chien 1996).

Bile acids have shown good efficacy in enhancing rectal absorption when complexed with or added to drug formulations. In human, INF-α, an antiviral, antineoplastic and immunoregulatory molecule, was not absorbed when administered rectally in a hydrophilic suppository, but when sodium ursodeoxycholate was incorporated into the suppository base, detectable levels were obtained (Lee et al. 1991; Lee 1991). By the same token, the effect of bile salts in insulin rectal absorption was investigated. Rectal administration with 5% sodium glycocholate produced a large increase in the effect of a 10 U/kg dose. Rectal and nasal administration reduced plasma glucose approximately half as effectively as intramuscular insulin in the presence of this bile salt (Aungst & Rogers 1988). This method of administration may be beneficial to those requiring only small doses of insulin or those uncomfortable with injection. Thus, it is clear that bile salts are effective promoters for rectal administration of insulin. The proposed mechanism of action involves enhanced membrane permeability, lipid solubilizing and the inhibition of proteolytic enzymes at the absorption site. However, rectal drug administration remains unfavorable and invasive and thus remains a major limitation for such a drug delivery system.
