Rectum, drug absorption

There are at least two common problems that can lead to drug loss following rectal administration. First, for effective absorption, the dosage form must be retained in the rectum. Thus if the dosage form or parts thereof are lost prematurely from the rectum, drug absorption will be substantially reduced. A study with children showed that when thiopentone suppositories were voided within 40 min, an effective plasma level was maintained for less than 2 h, whereas when the suppositories were retained, an effective level was maintained for about 24 h. 

Anatomy and Physiology of the Rectum and Its Role in Drug Absorption... 

Many physiological aspects affect drug absorption from the rectum (Table 7.1). Influential factors include the pH of the rectal contents, state of the mucus layer, volume and viscosity of rectal fluid, luminal pressure from the rectal wall on the dosage form, enzymatic and microbacterial degradation by rectal epithelium, presence of stools, and venous drainage differences within the rectosigmoid regions. 

Drug absorption may be variable depending upon the placement of the suppository or drug solution within the rectum. A portion of the drug dose may be absorbed via the lower hemorrhoidal veins, from which the drug feeds directly into the systemic circulation some drug may be absorbed via the superior hemorrhoidal veins, which feeds into the mesenteric veins to the hepatic portal vein to the liver, and metabolized prior to systemic absorption... 

Orally administered drugs are mainly absorbed in the small intestine (duodenum, jejunum, and ileum) and in the large intestine (colon) however, other regions, such as buccal cavity, stomach, and rectum, also can be considered potential sites for drug absorption. The various anatomical and physiological characteristics of each segment are briefly described in Table 1. 

Second, there is the possibility that the drug or some important excipients may interact with constituents of fecal matter or material fluid present in the rectum. This may reduce the drug absorption and diminish effectiveness. 

The smaller the drug molecule, the more readily it can be absorbed. For larger molecules, some type of facilitated transport or the use of penetration enhancers have been found to increase drug absorption from the rectum as well as from other delivery routes. 

Absorption from the rectum depends on various physiological factors such as surface area, blood supply, pH, fluid volume, and possible metabolism by microorganisms in the rectum. The rectum is perfused by the inferior and middle rectal arteries, whereas the superior, the middle, and the inferior rectal veins drain the rectum. The latter two are directly connected to the systemic circulation the superior rectal vein drains into the portal system. Drugs absorbed from the lower rectum are carried directly into the systemic circulation, whereas drugs absorbed from the upper rectum are subjected to hepatic first-pass effect. Therefore, a high-clearance drug should be more bioavailable after rectal than oral administration. The volume of fluid in the rectum, the pH of that fluid, and the presence of stool in the rectal vault may affect drug absorption. Because the fluid volume is... 

Drug absorption varies according to whether the drug is targeted to the upper colon, lower colon, or the rectum. 

The rate of drug absorption from the rectum is not influenced by ingestion of food or rate of gastric emptying. 

Some hydrophilic drugs such as antibiotics and peptide drugs are not easily absorbed from the rectum and absorption enhancers are required. 

The rectal route offers an alternative to the oral route of administration and offers some advantages in experimental work. Drug absorption from the rectum (of the... 

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