Intestinal epithelial cells drug transport across

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

Wils, P. Wamery, A. Phung-Ba, V. Legrain, S. Scherman, D., High lipophilicity decreases drug transport across intestinal epithelial cells, J. Pharmacol. Exp. Ther. 269, 654-658 (1994). 

Chao AC, Taylor MT, Daddona PE, Broughall M, Fix JA (1998b) Molecular weight-dependent paracellular transport of fluorescent model compounds induced by palmitoyl-carnitine chloride across the human intestinal epithelial cell line Caco-2. J Drug Targeting 6 37 13... 

Schipper, N. G., Varum, K. M., and Artursson, P. 1996. Chitosans as absorption enhancers for poorly absorbable drugs. 1. Influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial (Caco-2) cells. Pharm. Res., 13,1686. 

Palm, K., Luthman, K. and Artursson, P. (1999) Effect of molecular charge on drug transport across intestinal epithelial Caco-2 cell monolayers. Journal of Pharmacology and Experimental Therapeutics, 291, 435-443. 

Artursson P, C Magnusson. (1990). Epithelial transport of drugs in cell culture. II. Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells. J Pharm Sci 79 595-600. 

The successful application of in vitro models of intestinal drug absorption depends on the ability of the in vitro model to mimic the relevant characteristics of the in vivo biological barrier. Most compounds are absorbed by passive transcellular diffusion. To undergo tran-scellular transport a molecule must cross the lipid bilayer of the apical and basolateral cell membranes. In recent years, there has been a widespread acceptance of a technique, artificial membrane permeation assay (PAMPA), to estimate intestinal permeability.117118 The principle of the PAMPA is that, diffusion across a lipid layer, mimics transepithelial permeation. Experiments are conducted by applying a drug solution on top of a lipid layer covering a filter that separates top (donor) and bottom (receiver) chambers. The rate of drug appearance in the bottom wells should reflect the diffusion across the lipid layer, and by extrapolation, across the epithelial cell layer. 

Karlsson J, Kuo SM, Ziemniak J, Artursson P. Transport of celiprolol across human intestinal epithelial (Caco-2) cells mediation of secretion by multiple transporters including P-glycoprotein. Br JPharmacol 1993 110(3) 1009-1016. Cvetkovic M, Leake B, Fromm ME, Wilkinson GR, Kim RB. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 1999 27(8) 866-871. 

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