Intestinal permeation

Intestinal permeation describes the ability of drugs to cross the intestinal mucosa separating the gut lumen from the portal circulation. It is an essential... 

Lauterbach, F., Intestinal permeation of nonquatemary amines a study with telenzepine and pirenzepine in the isolated mucosa of guinea pig jejunum and colon, J. Pharmacol. Exp. Ther. 1987, 243, 1121-1130. 

Ewe K, Wanitscke R and Staritz M (1984) Intestinal Permeability Studies in Humans. In TZ Csaky (Ed.), Pharmacology of Intestinal Permeation II. New York, Springer-Verlag, pp 535-571. 

In addition to screening molecules for intestinal absorption, Caco-2 cells have also been used to study mechanisms of drug transport. For many compounds, intestinal permeation involves a transporter to either aid or limit transepithelial transport. The value of Caco-2 cells in this type of studies is due to the fact that these cells express various membrane transporters relevant to drug absorption.1719-23,28,30 However, when interpreting results of studies that involve carrier-mediated transport, discretion, and scaling factors may be required because of the difference in expression level of transporters between in vitro and in vivo systems.12 Another important consideration in carrier-mediated transport studies is that some transport systems in Caco-2 cells may achieve maximal expression level at different days in culture.17,21,38,74 Thus, validation of Caco-2 cells for mechanistic studies should include the identification of the time for optimal expression of transporters as well as the qualitative evaluation of the transporters to establish that they are representative of the native intestinal transporters. 

Thanou, M., Florea, B.I., Langermeyer, M.W.E., Verhoef, J.C., and Junginger, H.E., N-Trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (Caco-2 cells) and in vivo (rats), Pharm. Res., 17 27-31 (2000). 

Permeability of prodrugs will depend on the mechanism and (anatomical) site of conversion to the drug substance. When the prodrug-to-drug conversion is shown to occur predominantly after intestinal membrane permeation, the permeability of the prodrug should be measured. When this conversion occurs prior to intestinal permeation, the permeability of the drug should be detennined. Dissolution and... 

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. 

Hubbers, H. Rummel, W. "Intestinal Permeation" International Congress Series No. 391, Excerpta Medica Amsterdam, 1975 p 377. 

Singh et all studied the interaction of various barbiturates with polyethylene glycol 4000 and found that phe-nobarbital formed a complex with the glycol. The solubility of the complexed phenobarbital was much lower than the intrinsic solubility of phenobarbital in the absence of polyethylene glycol 4000. Utilizing the everted sac technique to measure the rate of intestinal permeability, they found that the decreased solubility greatly decreased the rate of permeation. The other three barbiturates studied, pentobarbital, barbital, and barbituric acid, did not interact with the polyethylene glycol 4000 and the inclusion of this material did not decrease their rates of intestinal permeation. 

The rate and extent of intestinal permeation is dependent on the physicochemical properties of the compound (see Sections 16.1.2 and 16.4.3) and the physiological factors. Drugs are mainly absorbed in the small intestine due to its much larger surface area and less tight epithelium in comparison to the colon [17]. The permeation of the intestine may be affected by the presence of an aqueous boundary layer and mucus adjacent to cells, but for a majority of substances the epithelial barrier is the most important barrier to drug absorption. The lipoidal cell membrane restricts the permeability of hydrophilic and charged compounds, whereas large molecules are restricted by the ordered structure of the lipid bilayer. 

Fig. 9. 12. Relationship between absorption rates of salicylic acid and ephedrine and bulk phase pH in the rat small intestine in vivo. Dashed lines represent curves predicted by the pH-partition theory in the absence of an unstirred layer. (From Winne D. The influence of unstirred layers on intestinal absorption in intestinal permeation. In Kramer M, Lauterbach F, eds. Workshop Conference Hoechest, vol 4. Amsterdam Excerpta Medica, 1977 58-64, with permission.)...

Winne D. The influence of unstirred layers on intestinal absorption in intestinal permeation. In Kramer M, Lauterbach F, eds. Workshop Conference Hoechest, vol 4. Amsterdam Excerpta Medica, 1977 58-64. 

Csaky, T. Z., 1984, Intestinal permeation and permeability An overview, in Pharmacology of Intestinal Permeation Z(Y. Z. Csaky, ed.), Spinger-Verlag, Berlin. 

Methyl-p-cyclodextrin/poly(isobutyl-cyanoacrylate) NPs coated with thiolated chitosan Intestinal permeation enhancement of docetaxel [256]... 

Mazzaferro S, Bouchemal K, Skanji R, Gueutin C, Chacun H, Ponchel G. Intestinal permeation enhancement of docetaxel encapsulated into methyl-p-cyclodextrin/ poly(isobutylcyanoacrylate)nanoparticles coated with thiolated chitosan. J Control Release. 2012 162(3) 568-74. 

Lindemann, B. In Parson, D.S., Kramer, M. (Eds.) Intestinal Permeation. Amsterdam Excerpta Medica 1976. 

Aungst B. 2002. Intestinal permeation enhancers. Journal of Pharmaceutical Sciences 429-442. 

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