How medicaments are absorbed through rectum?
- Insertion of a suppository into the rectum results in a chain of effects leading to the bioavailability of the drug. The sequence of events leading to drug absorption from the anorectal area can be represented as follows:
Drug in vehicle ? Drug in colon fluids ? Absorption through the rectal mucosa
- To be available for absorption, drugs must be released from the suppository and distributed by the surrounding fluids to sites of absorption. Depending on the character of its vehicle a suppository will either dissolve in the rectal fluid (water-soluble bases) or melt on the mucous layer (fatty bases).
- Independent of the vehicle type, drugs that are dissolved in the suppository diffuse out towards the rectal membranes. On the other hand, the suspended drugs first leave the vehicle (if it is water immiscible) under the influence of gravity or motility movements, and then start to dissolve in the rectal fluid. The dissolved drug molecules diffuse through the mucous layer into the epithelium forming the rectal wall to be absorbed by the tissues and eventually transported into the general circulation. The process of absorption is through passive diffusion throughout the whole GI tract for nearly all drugs.
- Blood supply, especially venous drainage, is important for the understanding of drug absorption. There is abundant vascularisation of the sub mucosal region of the rectum wall with blood and lymphatic vessels. A diagram of part of the rectal wall and the rectum venous drainage is shown below.
Rectal Venous Drainage Suppository Insertion
- As can be seen from the figure, there are three separate veins. Depending on the height at which absorption occurs in the rectum, the drug passes into the inferior, middle or superior haemorrhoidal veins. Inferior vein is nearest to the anus. The inferior and middle haemorrhoidal veins drain directly into the general circulation (via the inferior vena cava) and bypass the liver, while the superior haemorrhoidal vein drains into the hepatic portal vein which flows to liver. There are extensive anastomoses between the lower and upper hemorrhoidal veins.
- The lymphatic circulation also helps in absorbing a rectally administered drug and in diverting the absorbed drug from the liver. This means that drug molecules can enter the general circulation directly or by passing the strongly metabolizing liver. In the latter, only a proportion of the drug molecules (if they are of the high clearance type) enter the general circulation intact. Thus the bioavailability may be less than 100 %.
- It was once believed that medicaments from suppositories were largely transported by the inferior and middle haemorrhoidal veins and therefore rectal administration of a drug provided a means of avoiding degradation of the drug by liver and damage of the liver by drug. Indeed, the liver modifies many drugs chemically and thereby often reduces their systemic effectiveness.
- However, it appears that suppositories have the tendency to migrate to the upper rectum after administration. In such cases, only drug released from suppositories and absorbed at the lower rectum could avoid first pass effect and retain their therapeutic values.
- Hence, keeping the drug in lower part of the rectum is strongly advisable, specifically if the suppository is retained in the bottom one third of the rectal vault.