Rectal absorption potential

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

In view of their solubilizing effects and also their potential to change membrane permeability, surfactants have been considered as absorption enhancers, again mostly in animals. Polyoxyethylene ethers have been shown to enhance gastric or rectal absorption of linco-mycin, penicillin, cephalosporins, and fosfomycin in rats and rabbits. In rats, colonic absorption of interferon-alpha is increased from 3 to 8% by polyoxyethylene esters of oleic acid and oleic acid glycerides. 

Rectal solutions have water or oil as a vehicle. If necessary to enhance the solubility of poorly soluble active substances, aqueous rectal solutirms may contain cosolvents, such as ethanol and propylene glycol. However, cosolvents and surfactants should only be used in limited amounts because of the potential irritation and the defecation reflex they may cause. For the rectal absorption of active substances from enemas the same mechanisms as for suppositories apply. A major advantage of a rectal solution over a suppository may be the fact that the active substance is already in a dissolved state which may increase the absorption rate. Increasing the volume of a rectal solution to dissolve a poorly water-soluble active substance will enhance the dissolution rate and thereby increase the absorption rate. Because of the higher volume more active substance will be dissolved and the membrane surface over which absorption occurs, is increased as well. 

Possible noninvasive routes for delivery of proteins include nasal, buccal, rectal, vaginal, transdermal, ocular, oral, and pulmonary. For each route of delivery there are two potential barriers to absorption permeability and enzymatic barriers. All of the... 

Taking broken, chewed, or crushed tablets could lead to the rapid release and absorption of a potentially fatal dose of oxycodone. OxyContin is not indicated for rectal administration. Data from a study involving 21 normal volunteers show that OxyContin tablets administered per rectum resulted in an AUC 39% greater and a Cmax... 

An important issue that has been recognized recently concerns the potential adverse effect of absorption enhancers on the rectal mucosa, as shown in rats after a single application [61,62], Safety evaluation of the applicability of absorption enhancers is imperative. In clinical application, medium-chain fatty acids such as sodium caprate are used only for suppositories containing antibiotics [36],... 

Furthermore, the permeation-enhancing effects of NO donors seem to be strongly dose-dependent. Utoguchi et al. (1998) reported that the absorptionenhancing effect of S-nitroso-A-acetyl-penicillamine for rectal insulin absorption was dose-dependent over the range of 0.25-4.0 mg in rats. Similarly, Salzman et al. (1995) demonstrated that incubation with sodium nitroprusside resulted in a concentration-dependent increase in the transepithelial transport of fluorescein sulphonic acid in Caco-2 cells. To our knowledge the potential of NO donors for oral macromolecular delivery, however, has so far not been tested in a valid animal model. 

The presence of medium chain fatty acids and glycerides in food products has stimulated interest in their potential utility as absorption enhancers. Some fatty acids and glycerides have been shown to increase drug absorption under a variety of conditions, almost always in animals and in most cases after rectal dosing. However, some studies have yielded positive results after oral dosing. Oral insulin bioavailability was increased to 9-13% relative to IM administration by a mixture of sodium dodecanoate and cetyl alcohol. Aftiraxone absorption was enhanced by glyceryl-1-monooctanoate after oral, duodenal, and rectal administration to animals. 

The choice of rectally administered steroid is a subject of debate, as there is varying potential for systemic steroid absorption with different products. Although many steroids have been administered rectally, certain agents such as betamethasone-17-valerate, beclomethasone dipropionate, prednisolone metasulfobenzoate, prednisolone-21-phosphate, and budesonide have been used in attempts to reduce systemic steroid effects. Systemic side effects may be the least severe with beclomethasone dipropionate, because... 

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