Absorption enhancers enhancing mechanism

Tomita, M., I. M. Hayash, and S. Awazu. Absorption-enhancing mechanism of EDTA, caprate, and decanoylcamitine in Caco-2 cells.,... 

Uchiyama, T., et al. 1999. Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers Their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-D-maltopyranoside. J Pharm Pharmacol 51 1241. 

Tomita M, Hayashi M, Awazu S (1995) Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells. J Pharmacol Exp Ther 272 739-743 Uchiyama T, Yamamoto A, Hatano H, Fujita T, Muranishi S (1996) Effectiveness toxicity screening of various absorption enhancers in the large intestine intestinal absorption of phenol red and protein and phospholipid release from the intestinal membrane. Biol Pharm Bull 19 1618-1621... 

Therefore, the absorption of stearic acid was considerably enhanced due to the presence of DIMES in bile duct-ligated rats. In all probability, the absorption enhancing mechanism of DIMES differs from that of sodium deoxycholate. 

LeCluyse. In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcamitine.,... 

Muranishi, S., Yamamoto, A., Mechanisms of absorption enhancement through gastrointestinal epithelium, in Drug Absorption Enhancement, de Boer, A. G. (ed.), Harwood Academic Publishers, 1994, 67-100. 

Hochman, J., Artursson, P., Mechanisms of absorption enhancement and tight junction regulation, J. Controlled Release 1994, 29, 253-267. 

Sjosteom, M., Lindfors, L., Ungell, A. L., Inhibition of binding of an enzymatically stable thrombin inhibitor to lumenal proteases as an additional mechanism of intestinal absorption enhancement, Pharm. Res. 1999, 26, 74-79. 

In situ intestinal mechanisms (e.g., polarity in transport) Evaluation of absorption enhancing strategies on a mechanistic basis Well-defined absorptive area Good oxygenation Closest model to in vivo Implies anesthesia and surgery... 

Caco-2 cells have been valuable in the estimation of drug absorption potential, transport mechanisms, and effect of permeation enhancers on transepithelial transport.35,39,53,67-69,78-81 Owing to the sensitivity of the cells and the limited solubility of new molecular entities, Caco-2 permeability studies are routinely done with relatively low concentration of compounds. One way to increase the solubility of these compounds is to use organic solvents. The low tolerability of Caco-2 cells to organic solvents limits the use of this approach in permeability studies. 

Marttin, E., Verhoef, J. C., and Merkus, F. W. H. M. 1998. Ef cacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein dtdgsug Target. 6 17-36. 

Lindmark, T., et al. 1997. Mechanism of absorption enhancement in humans after rectal administration of ampicillin in suppositories containing sodium caprate. Pharm Res 14 930. 

Lindmark, T., T. Nikkila, and P. Artursson. 1995. Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 275 958. 

Takahashi, H., et al. 1997. The enhancing mechanism of capric acid (CIO) from a suppository on rectal drug absorption through a paracellular pathway. Biol Pharm Bull 20 446. 

The most efficient rectal absorption enhancers, which have been studied, include surfactants, bile acids, sodium salicylate (NaSA), medium-chain glycerides (MCG), NaCIO, enamine derivatives, EDTA, and others [45 17]. Transport from the rectal epithelium primarily involves two routes, i.e., the paracellular route and the transcellular route. The paracellular transport mechanism implies that drugs diffuse through a space between epithelial cells. On the other hand, an uptake mechanism which depends on lipophilicity involves a typical transcellular transport route, and active transport for amino acids, carrier-mediated transport for (3-lactam antibiotics and dipeptides, and endocytosis are also involved in the transcellular transport system, but these transporters are unlikely to express in rectum (Figure 8.7). Table 8.3 summarizes the typical absorption enhancers in rectal routes. 

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