Colonic absorption

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

For most formulations, colonic absorption represents the only real opportunity to increase the interval between dosing. Transit through the lower part of the gut is quoted at around 24 hr, but in reality only the ascending colonic environment has sufficient fluid to facilitate dissolution. The supplementa-... 

Thus, the apparent membrane permeability characteristics of hydrophilic compounds listed in Table 3.4 indicate that colonic epithelium is different from small intestinal epithelium in selectivity, or size or density distribution of the paracellular pathway. This is further complicated because of the possible involvement of unidentified carriers or channels for some compounds, as suggested for glycerol and D-xylose. However, the colon-to-SI ratios of the apparent membrane permeability are generally comparable with (or lower than) those calculated considering the morphological surface area, suggesting that such factors are not in favor for colonic absorption in most cases. Matching... 

Log D accounts for where the "dose" is, so to speak. The distribution depends on the pKa as well as the pH of the medium. The advantage of using log D is that it incorporates these factors, so, for simple processes such as absorption, distribution coefficients "ej lain" the whole process. An example from our earlier work ( ) is the colonic absorption of acids ranging from phenols to strong carboxylic acids. The absorption rate is given by an equation involving only log D terms. 

Emollient Mineral oil 6-8 Colon Retards colonic absorption of fecal water softens stool... 

Hydrocortisone enemas, foam, or suppositories are used to maximize colonic tissue effects and minimize systemic absorption via topical treatment of active inflammatory bowel disease in the rectum and sigmoid colon. Absorption of hydrocortisone is reduced with rectal administration, although 15-30% of the administered dosage is still... 

Sakai, K., et al. 1986. Contribution of calcium ion sequestration by polyoxyethylated nonionic surfactants to the enhanced colonic absorption of p-aminobenzoic acid. J Pharm Sci 75 387. 

Suzuka, T., et al. 1986. Effects of phenothiazines and /V-(6-aminohexyl)-5-chloro-l-naphthalene-sulfonamide on rat colonic absorption of cefmetazole. J Pharmacobiodyn 9 460. 

Cundy, K. C., Annamalai, T., Bu, L., et al. XP13512 [( )-l-([(a-isobutanoyloxyethoxy) carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys. J. Pharmacol. Exp. Ther. 311 324-333, 2004. 

The scientific rationale of drug absorption from the colon was developed some years ago as exemplified by a series of publications [4-8], The extent of colonic absorption of drugs has been controversial in the literature, although this only parallels the controversies regarding the bioavailabilities of such drugs in general [10]. 

For some drugs that, for physiological and anatomical reasons, mainly follow a passive absorption mechanism, a satisfactory colonic absorption was demonstrated. Similar absorption rates from the small and large intestine were found for oxprenolol, metoprolol, isosorbide-5-mononitrate, and glibenclamide [9], It has also been known for many years, that some lipophilic vitamins, as well as bile salts and some steroids, that undergo enterohepatic circulation show satisfactory colonic absorption [2],... 

Obviously, satisfactory colonic absorption of the drug to be delivered is a sine qua non for the successful development of a colonic drug delivery system. However, situations exist when even reduced absorption from the large intestine (compared with the small intestine) would still justify colonic delivery, for instance in the case of a peptide drug that would otherwise be efficiently digested in the small intestine. 

Satisfactory colonic absorption is also an important prerequisite for the reliable function of prolonged action dosage forms. 

It must be taken into account that the intestinal microflora may change transiently because of illness, medication (e.g., antibiotics), or substantial changes in food intake. However, the microflora has an intrinsic mechanism of regulation that is able to restore normal standards within a relatively short time [37-39], As mentioned before, although the colonic absorption conditions are relatively good in the colon ascendens, they are, even under normal conditions, not as favorable as in the small intestine and become increasingly less favorable with increasing viscosity and consistency. 

To describe the relationship between colonic absorption rate constants and the lipophilicity of xenobiotics, the hyperbolic equation proposed by Wagner applies [2]. 

Dodecylmaltoside increased the small intestinal and colonic absorption of phenol red in rats without causing membrane protein and phospholipid release (Yamamoto et al. 1996 Uchiyama et al. 1996). These results, however, are not in agreement with an in vitro study showing a significant protein and phospholipid release from rat jejunum and colon when dodecylmaltoside is applied in the same concentration (Yamamoto et al. 1997). 

Longer chain fatty acids are also effective as intestinal permeation enhancers. Morishita et al. (1998), for instance, could significantly increase the in situ colonic absorption of insulin in rats utilizing emulsions (w/o/w) containing oleic, linoleic or linolenic acid. 

Rivera TM, Leone-Bay A, Paton DR, Leipold H, Baughman RA (1997) Oral delivery of heparin in combination with sodium N-[8-(2-hydroxybenzoyl) aminojcaprylate pharmacological considerations. Pharm Res 14 1830-1834 Sakai K, Kutsuna TM, Nishino T, Fujihara Y, Yata N (1986) Contribution of calcium ion sequestration by polyoxyethylated nonionic surfactants to the enhanced colonic absorption of p-aminobenzoic acid. J Pharm Sci 75 387-390 Sakai M, Imai T, Ohtake H, Azuma H, Otagiri M (1997) Effects of absorption enhancers on the transport of model compounds in Caco-2 cell monolayers assessment by confocal laser scanning microscopy. J Pharm Sci 86 779-785... 

Ishizawa, T., M. Hayashi and S. Awazu (1987). Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat. J Pharm Pharmacol 39 892-895. 

For most formulations, colonic absorption represents the only real opportunity to increase the interval between doses. Transit through the lower part of the gut is quoted at about 24h, but in reality only the ascending colonic environment has sufficient fluid to facilitate dissolution. In the cecum, the fermentation of soluble fiber produces fatty acids and gas [33].The gas rises into the transverse colon and can form temporary pockets, restricting access of water to the formulation. Consequently, distal release of drug is associated with poor spreading, reduced surface area, and restricted absorption. In the colon, water availability is also low past the hepatic flexure, as the ascending colon is extremely efficient at water absorption [34],... 

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