Abstract
Oral drug administration is the most convenient method to administer drugs, particularly in the treatment of chronic diseases. This preference is generally the case, even when the site of drug action is beyond the gastrointestinal tract (GI), requiring the drug to be systemically available. For systemic drug availability, drug dosing via the oral route requires the drug to exhibit sufficient gastrointestinal absorption. Two components of drug absorption from solid oral-dosage forms (e.g., tablets, capsules) are: (1) drug dissolution from the dosage form, which results in the drug being in solution within the gut lumen, and (2) drug permeation across the GI wall. In this chapter, elements of GI drug permeability are discussed, with special emphasis on the enterocyte and the in vitro Caco-2 cell model. Included is a discussion of the lipid plasma membrane, in vitro drug permeability and its relation to in vivo permeability, and a discussion of future research directions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kenyon CJ, Brown F, McClelland GR, Wilding IR. The use of pharmacoscintigraphy to elucidate food effects observed with a novel protease inhibitor (saquinavir). Pharm Res 1998; 15: 417–422.
Lennernas H. Human intestinal permeability. J Pharm Sci 1998; 87: 403–410.
Friedman MH. Principles and Models of Biological Transport. Berlin, Springer-Verlag, 1986: 216.
Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 1977; 59: 221–226.
Pinto M, Robine-Leon S, Appay MD, et al. Enterocytic like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture. Biol Cell 1983; 47: 323–330.
Hidalgo IJ, Raub TJ, Borchardt RT. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 1989; 96: 736–749.
Hidalgo IJ, Borchardt RT. Transport of bile acids in a human intestinal epithelial cell line, Caco-2. Biochim Biophys Acta 1990; 1035: 97–103.
Yu H, Cook TJ, Sinko PJ. Evidence for diminished functional expression of intestinal transporters in Caco-2 cell monolayers at high passages. Pharm Res 1997; 14: 757–762.
Walter E, Janich S, Roessler BJ, et al. HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans. J Pharm Sci 1996; 85: 1070–1076.
Pontier C, Pachot J, Botham R, Lenfant B, Arnaud P. HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption: role of the mucus layer. J Pharm Sci 2001; 90: 1608–1619.
Artursson P, Ungell AL, Lofroth JE. Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments. Pharm Res 1993; 10: 1123–1129.
Tsuji A, Tamai I. Carrier-mediated intestinal transport of drugs. Pharm Res 1996; 13: 963–977.
Yang C, Tirucherai GS, Mitra AK. Prodrug based optimal drug delivery via membrane transporter/receptor. Expert Opin Biol Ther 2001; 1: 159–175.
Han H, de Vrueh RL, Rhie JK, et al. 5’-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm Res 1998; 15: 1154–1159.
Anderle P, Rakhmanova V, Woodford K, et al. Messenger RNA expression of transporter and ion channel genes in undifferentiated and differentiated Caco-2 cells compared to human intestines. Pharm Res 2003; 20: 3–15.
Chu XY, Sanchez-Castano GP, Higaki K, et al. Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter. J Pharmacol Exp Ther 2001; 299: 575–582.
Chandler CE, Zaccaro LM, Moberly JB. Transepithelial transport of cholyltaurine by Caco-2 cell monolayers is sodium dependent. Am J Physiol 1993; 264: G1118 - G1125.
Putnam WS, Ramanathan S, Pan L, et al. Functional characterization of monocarboxylic acid, large neutral amino acid, bile acid and peptide transporters, and P-glycoprotein in MDCK and Caco-2 cells. J Pharm Sci 2002; 91: 2622–2635.
Anderle P, Niederer E, Rubas W, et al. P-Glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: the influence of culturing conditions and drug exposure on P-gp expression levels. J Pharm Sci 1998; 87: 757–762.
Taipalensuu J, Tornblom H, Lindberg G, et al. Correlation of gene expression of ten drug efflux proteins of the ATP- binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 2001; 299: 164–170.
Sun D, Lennernas H, Welage LS, et al. Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs. Pharm Res 2002; 19: 1400–1416.
Schmiedlin-Ren P, Thummel KE, Fisher JM, et al. Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3. Mol Pharmacol 1997; 51: 741–754.
Geick A, Eichelbaum M, Burk O. Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 2001; 276: 14581–14587.
Lentz KA, Hayashi J, Lucisano LJ, Polli JE. Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system. Int J Pharm 2000; 200: 41–51.
Liang E, Chessic K, Yazdanian M. Evaluation of an accelerated Caco-2 cell permeability model. J Pharm Sci 2000; 89: 336–345.
Irvine JD, Takahashi L, Lockhart K, et al. MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J Pharm Sci 1999; 88: 28–33.
Proulx P. Structure-function relationships in intestinal brush border membranes. Biochim Biophys Acta 1991; 1071: 255–271.
Brasitus TA, Dudeja PK. Effect of hypothyroidism on the lipid composition and fluidity of rat colonic apical plasma membranes. Biochim Biophys Acta 1988; 939: 189–196.
Xiang TX, Chen J, Anderson BD. A quantitative model for the dependence of solute permeability on peptide and cholesterol content in biomembranes. J Membr Biol 2000; 177: 137–148.
Rege BD, Kao JPY, Polli JE. Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers. Eur J Pharm Sci 2002; 16: 237–246.
Artursson P, Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem Biophys Res Commun 1991; 175: 880–885.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer Science+Business Media New York
About this chapter
Cite this chapter
Polli, J.E., Balakrishnan, A., Seo, P.R. (2004). Human Intestinal Cellular Characteristics and Drug Permeability. In: Lu, D.R., Øie, S. (eds) Cellular Drug Delivery. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-745-1_10
Download citation
DOI: https://doi.org/10.1007/978-1-59259-745-1_10
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-455-5
Online ISBN: 978-1-59259-745-1
eBook Packages: Springer Book Archive