Bioavailability Through Rectal Administration: Suppositories & Enemas

Have you ever wondered why suppositories and enemas work so well? That would be because of the bioavailability available through the rectum. In this article you can find out about the anatomy of the rectum and how this is possible. [Throughout the article, when “substance” is mentioned, it is in reference to both suppositories and liquid enemas.]

What is Bioavailability?

Bioavailability is the extent at which a nutrient, substance, or medication becomes completely available to the desired area of the body. (1)

Why the Rectum?

When it comes to the human body, the rectum is the final portion of the large intestine. It starts at the end of the sigmoid colon and ends at the anal canal. Compared to other parts of the gastrointestinal tract, the rectum generally has a constant and static environment. This environment includes a small surface area for absorption along with a mucosal surface that includes a single layer of columnar cells to form the epithelium. Within the epithelium, there are goblet cells interspersed to assist with secreting mucus. (2)

This leads us into how the rectum is drained. This process happens thanks to rectal and lymphatic vessels. These drainage processes happen in three places: the superior, inferior, and middle rectal veins. The superior rectal vein drains the upper part of the rectum into the portal vein, which passes the blood through the liver before it reaches the systemic circulation. While this is occurring, the inferior and middle rectal veins drain the lower part of the rectum into the inferior vena cava, which goes directly into the systemic circulation. Although these are separate drainage systems, the veins are connected. This direct pathway into the systemic circulation is key to having increased bioavailability. (2)

Oral vs. Rectal Administration

Generally, the oral route is preferred by users - it's easy, convenient, and non-invasive. The major absorption site is the small intestine. The small intestine has a much larger surface area than that of the rectum, but oral administration has its downfalls. It can have an unpleasant taste, cause gastric irritation, and can even go through high first-pass metabolism in the intestine and liver, which is known to decrease bioavailability. The gastrointestinal tract’s physiological environment has been known to affect the stability, solubility, and permeability of substances. Therefore, oral administration is less effective for many substances that are affected by the environment of the gastrointestinal tract. (2)

What about the rectal route? Rectally administering a substance is helpful for those that have poor stability, solubility, or permeability with oral administration. It is also a perfect alternative for the times when oral ingestion is compromised due to nausea, vomiting, and swallowing difficulties. Although the rectum has a smaller surface area, it has a relatively stable and constant environment that favors a reproducible absorption process. Along with these factors, through the rectum, substances can also partially bypass the liver following systemic absorption, which reduces first-pass metabolism. (2)

Even though it is observed that the rectum has less of that hepatic first-pass metabolism, it is still important which site is used because the site can affect the amount of the substance that reaches the systemic circulation. Generally, the upper part of the rectum absorbs and transports substances to the liver and first-pass metabolism occurs. When a substance is delivered through the lower rectum, it is then absorbed and transported directly to the systemic circulation for maximum bioavailability. If a substance happens to be susceptible to first-pass metabolism then this is a very important key factor. Even with the possibility of absorption through the upper part, it has been reported that approximately 50% of a substance that is absorbed from the rectum will bypass the liver, which in turn reduces first-pass metabolism. (2)

Conclusion

Not every person is identical anatomically and, therefore, there are other factors that can affect the bioavailability of substance administration in each person’s body. However, these findings do conclude that rectal administration will still provide high bioavailability and can be a useful administration method for substances susceptible to high hepatic first-pass metabolism, have trouble absorbing in the upper gastrointestinal tract, easily degrade and are unstable in the gastrointestinal tract, or have a localized action in the rectum or surrounding area. Thanks to the direct pathway into the systemic circulation, this method also allows for absorption into the entire body efficiently. (2)

Glossary

Bioavailability: The extent at which a nutrient, substance, or medication becomes completely available to the desired targeted area of the body. (1)
First-pass metabolism: This is a phenomenon in which a substance gets metabolized at a specific location in the body and then results in a reduced concentration of the active substance upon reaching its site of action or the systemic circulation. (6)
Hepatic: Of or relation to the liver. (5)
Hepatic portal vein: The vein that receives blood from the body, including the abdominal tract, pancreas, gallbladder, and spleen, and transports it to the liver for filtration and processing. (5)
Inferior vena cava: This vessel returns blood to the heart from the abdominal walls and viscera below the diaphragm. (4)
Systemic circulation: The circulatory system that moves oxygenated blood from the heart to the rest of the body and loops the deoxygenated blood back to the heart. (3)

References