Rectal drug administration

1. Rectal drug administration Dr Mohammad Issa

2. Rectal drug administration advantages • a relatively large dosage form can be accommodated in the rectum • the rectal route is safe and convenient for elderly and young patients • drug dilution is minimized as the residual fluid volume is low • the rectum is generally empty • absorption adjuvants have a more pronounced effect than in the upper gastrointestinal tract • degradative enzymes in the rectal lumen are at relatively low concentrations • therapy can easily be discontinued • first-pass elimination of drug by the liver is partly avoided

3. Barriers for drug absorption following rectal administration • If the drug is administered as a suppository, melting or liquefaction of the base has to occur and the degree of this will partly determine the spreading of the dose through the rectum. The drug must then dissolve in the limited rectal fluid available, which has been estimated to be between 1 and 3 ml • The amount of drug available for absorption can be further reduced by degradation by luminal contents, adsorption to luminal contents and defaecation. The drug must then diffuse across the unstirred water and mucous layers adjacent to the epithelium

4. Drug absorption and avoidance of first-pass metabolism • Drugs may be absorbed across the epithelial cell or via tight junctions, and it is believed that only passive transport occurs • Venous return from the colon and upper rectum is via the portal vein to the liver. If a drug is delivered to the upper part of the rectum, it is transported into the portal system, and is therefore subject to first pass metabolism in the liver. • The only way of avoiding first-pass metabolism is to deliver the drug to the lower part of the rectum • A 100% increase in the availability of lignocaine was demonstrated when administered rectally rather than orally, and it was calculated that the mean fraction of the rectally administered dose escaping first-pass metabolism was 57%

6. Dosage forms for rectal delivery • Suppositories: are normally either solid suspensions or solid emulsions • Rectally administered gelatin capsules: can contain liquid formulations • Enema: Micro-enemas have a volume of between 1 and 20 ml and macro enemas 50 ml or more, both of which may be administered as either solutions or suspensions

7. Adjuvants and enhancers • Transport from the rectal epithelium primarily involves two transport processes: paracellular and transcellular routes. • As in other parts of the gut, the opening of tight junctions by absorption enhancers has been extensively investigated • Putative enhancers include enamine derivatives, salicylates, calmodulin inhibitors, surfactants, chelating agents, fatty acids and lectins

8. Adjuvants and enhancers • Bioavailability of a small peptide such as vasopressin is increased to nearly 30% in the presence of sodium taurodihydrofusidate • It should always be borne in mind that the enhancement via the paracellular route is non-selective, with the risk of absorption of bacterial endotoxins caused by lysis of bacterial cell walls

9. Therapeutic agents administered rectally • Anticonvulsants • Preoperative medication and induction of anaesthesia • Analgesics and antiarthritics • Antiemetics • Antibacterial agents • Xanthines • Drugs in inflammatory bowel disease • Cardiovascular active drugs