Rectal cavity

In this section several recently published studies on the interaction of nonionic surfactants with a variety of biological systems, including enzymes, bacteria, erythrocytes, leukocytes, membrane proteins, low density lipoproteins and membranes controlling absorption from the gastrointestinal tract, nasal and rectal cavities, will be assessed. This is a selective account, work having been reviewed that throws light on structure-activity relationships and on mechanisms of surfactant action. 

The promotion of insulin absorption from the rectal cavity has been studied by Touitou et a, (9 ), Figure 3 illustrates the marked influence of ethylene oxide chain length in the Ci2 series and of alkyl chain length in the CxEg series. This striking demonstration of the structural dependence of activity is indicated with the loss of activity when the Ci2E25 C12E4Q compounds are used. Here appears to be the most active... 

To achieve a reasonable degree of absorption, peptide and protein pharmaceuticals may need permeation enhancers to promote passage across mucosal cells. Another concern is that studies of insulin and enkephalin in animals suggest that protease activity may be high, especially in the rectal cavity [5,6]. On the other hand, the density of lymphatic vessels and drainage therein at these sites may be advantageous compared with other routes of administration. 

Unlike the small intestine and upper colon, the vasculature draining the rectal cavity does not totally direct the blood supply to the liver. The lower and middle hemorrhoidal veins of the rectum bypass, at least... 

Dmgs administered by the rectal route in suppositories are placed in intimate contact with the rectal mucosa, which behaves as a normal lipoidal barrier. The pH in the rectal cavity lies between 7.2 and 7.4, but the rectal fluids have little buffering capacity. As with topical medication, the formulation of the suppository can have marked effects on the activity of the drug. Factors such as retention of the suppository for a sufficient duration of time in the rectal cavity also influence the outcome of therapy the size and shape of the suppository and its melting point may also determine bioavailability. 

Figure 9.52 shows the blood supply to the rectal area. The main artery to the rectum is the superior rectal (haemorrhoidal) artery. Veins of the inferior part of the submucous plexus become the rectal veins, which drain to the internal pudendal veins. Dmg absorption takes place through this venous network. Superior haemorrhoidal veins connect with the portal vein and thus transport dmgs absorbed in the upper part of the rectal cavity... 

Various transport processes used by low molar mass drugs to cross the epithelial barrier lining oral, buccal, nasal, vaginal, and rectal cavities include passive diffusion, carrier-mediated transfer systems, and selective and nonselective endocytosis. Additionally, polar materials can also diffuse through the tight junctions of epithelial cells (the paraceUular route). Evidence also exists that suggests that macromolecules (particulate... 

The pharmacist should have anticipated the bio-pharmaceutical consequences of the physico-chemical properties of oxcarbazepine. The drug is classified as a Class II substance for oral application. Logically, lack of adequate solubility is even more evident for the rectal administration as the volume of rectal fluid is limited (see Table 17.1). With an aqueous solubility of approximately 300 mg/L, the solubUity of the substance in the lipophilic base of the suppositories would certainly not be higher than 9.5 mg/mL (being a direct consequence of the value of the log P = 1.5 of oxcarbamazepine). This means that oxcarbazepine is not dissolved in the lipid but dispersed as crystals, which settle from the molten suppository once introduced in the rectal cavity. The amount of rectal liquid is limited and therefore a saturated solution will exist which involves only less than 1 mg dissolved oxcarbamazepine. Low solubility yields a low concentration and hence a low driving force for diffusion to occur. As a consequence, the rate of absorption is relatively low. This slow release may lead to hardly any uptake, due to defecation within several hours after insertion. 

The rectal cavity has the potential of convenient access and easy administration of suppositories or gels, although patient acceptance of rectal delivery is low in some cultures. It has a limited surface area (de Boer et al, 1992) and relatively high proteolytic activity (Lee et al, 1987), but with respect to administration of insulin the rectal route offers the particular physiological advantage of potential delivery, via the upper rectal veins, into the portal system. This would mimic the natural secretion of insulin and result in reduced peripheral hyperinsulinemia. However, nearly two-thirds of the insulin absorbed firom the rectum reaches the general circulation via the lymphatic pathway (Caldwell et al, 1982). 

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