The rectum is the ending portion of the large intestine, approximately 15 cm long,
from the colon to the anal sphincters. It can be used as a drug delivery route for both
local and systemic effects. Rectal medication may be in suppository form or in liquid form to be administered as a retention enema.
The rectal epithelium is composed of non-keratinized and villi-free cells, presenting a surface available for absorption of around 200 – 400 cm2, significantly smaller than the duodenal mucosa. In general, the rectum is empty, occupied only by a few milliliters of fluid with pH ranging from 6 to 8, without buffer capacity, and very viscous due to the presence of mucin.
This characteristic of the rectum hinders drug absorption since it imposes serious limitations to the drug dissolution process.
The rectal area is perfused by the hemorrhoidal arteries, which in turn drain into the upper, middle, and lower hemorrhoidal veins. The last two converge in the hypogastric vein and from there they access the inferior vena cava, which carries their contents to the heart.
On the other side, the superior hemorrhoidal vein joins the mesenteric circulation, which feeds into the portal vein and from there to the liver. This is why the absorption of drugs through the rectal epithelium is often erratic and variable, since depending on the specific area where it occurs, part of the absorbed amount directly access the systemic circulation while another fraction suffer first pass metabolism.
There are several scenarios in which the rectal route of drug administration may become the route of choice due to one of the following characteristics:
1. Applicable in cases of nausea, vomiting, and inability to swallow (unconscious patients), as well as in the presence of diseases of the upper gastrointestinal tract that affect oral drug absorption.
2. Suitable for formulations with unpleasant taste (a particularly important factor in children).
3. Allows achieving rapid systemic effects by giving a drug in a suitable solution (as an alternative to injection), with the additional advantage that such effect can be rapidly terminated in cases of toxicity or overdose.
4. The absorption rate of the drug is not influenced by food or gastric emptying.
5. Part of the metabolism of both enteric and first-pass hepatic elimination is avoided, which may result in a significant increase in bioavailability of extensively metabolized drugs (such as lidocaine).
6. Avoids the contact of the drug with the aggressive conditions of the upper gastrointestinal tract.
7. Preferred route when drugs are administered to relieve constipation or hemorrhoids.
Some drawbacks associated with rectal administration of pharmaceutical products, include:
1. The interruption of the absorption process by defecation, which can occur especially when the drug is irritant.
2. Absorption can be highly irregular and incomplete.
3. The reduced surface area may limit absorption, in the same way that the low volume of rectal fluids can lead to incomplete dissolution of the drug.
4. It is possible the degradation of certain drugs by microorganisms in the rectum.
5. Patient adherence may be a problem.