Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs' lipophilicity and molecular weight

European Journal of Pharmaceutical Sciences

Volumn 6, Issue 4, 1998, Pages 313-319

  Camenisch, Gian ^a,b   Alsenz, Jochem ^a   Van De Waterbeemd, Han ^a,c   Folkers, Gerd ^b  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b ETH ZURICH   (Switzerland)

^c PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Absorption prediction; Caco 2 cell monolayers; Lipophilicity; Membrane permeation; Molecular weight; Passive diffusion

Indexed keywords

ADRENALIN; ALPRENOLOL; ATENOLOL; CORTICOSTERONE; DEXAMETHASONE; DILTIAZEM; FELODIPINE; FUROSEMIDE; GUANABENZ; IMIPRAMINE; LIDOCAINE; MANNITOL; METOPROLOL; MIBEFRADIL; NITRENDIPINE; OCTANOL; OLSALAZINE; PRACTOLOL; PROPRANOLOL DERIVATIVE; SALAZOSULFAPYRIDINE; SAQUINAVIR; SULPIRIDE; TERBUTALINE; TESTOSTERONE; THEOPHYLLINE; TIACRILAST; UNINDEXED DRUG; VERAPAMIL; WARFARIN; WATER; CYP3A PROTEIN, HUMAN; CYTOCHROME P450; DRUG; GLYCOPROTEIN P; LIPID;

ARTICLE; CELL STRAIN CACO 2; CONTROLLED STUDY; DRUG DIFFUSION; DRUG DISTRIBUTION; DRUG PENETRATION; EPITHELIUM CELL; HUMAN; HUMAN CELL; LIPOPHILICITY; MEMBRANE TRANSPORT; MOLECULAR SIZE; MOLECULAR WEIGHT; MONOLAYER CULTURE; PRIORITY JOURNAL; ALGORITHM; CELL MEMBRANE PERMEABILITY; CHEMISTRY; DIFFUSION; DRUG EFFECT; METABOLISM; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION;

ALGORITHMS; CACO-2 CELLS; CELL MEMBRANE PERMEABILITY; CHEMISTRY, PHYSICAL; CYTOCHROME P-450 ENZYME SYSTEM; DIFFUSION; HUMANS; LIPIDS; MOLECULAR WEIGHT; P-GLYCOPROTEINS; PHARMACEUTICAL PREPARATIONS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032189375     PISSN: 09280987     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0928-0987(97)10019-7     Document Type: Article

References (36)

1. Adson, A., Raub, T.J., Burton, P.S., Barsuhn, C.L., Hilgers, A.R., Audus, K.L., Ho, N.F.H., 1994. Quantitative approaches to delineate paracellular diffusion in cultured epithilial cell monolayers. J. Pharm. Sci. 83, 1529-1536.
2. Anderberg, E.K., Nyström, C., Artursson, P., 1991. Epithelial transport of drugs in cell culture. VII: Effects of pharmaceutical surfactant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells. J. Pharm. Sci. 81, 879-887.
3. Artursson, P., 1991. Cell cultures as models for drug absorption across the intestinal mucosa. Crit. Rev. Ther. Drug Car. 8, 305-330.
4. Artursson, P., Karlsson, J., 1991. Correlation between oral drug absorption in humans and apparent permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 175, 880-885.
5. Artursson, P., Palm, K., Luthman, K., 1996. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv. Drug Deliv. Rev. 22, 67-84.
6. Artursson, P., Ungell, A.L., Löfroth, J.E., 1993. Selective paracellular permeability in two models of intestinal absorption: Cultured monolayers of human intestinal epithelial cells and rat intestinal segments. Pharm. Res. 10, 1123-1129.
7. Avdeef A., 1996. Assessment of distribution-pH profiles. In: Pliska V., Testa B., Van de Waterbeemd H. (Eds.), Lipophilicity in Drug Action and Toxicology. VCH, Weinheim, pp. 109-139.
8. Burton, P.S., Conradi, R.A., Ho, N.F.H., Hilgers, A.R., Borchardt, R.T., 1996. How structural features influence the biomembrane permeability of peptides. J. Pharm. Sci. 85, 1336-1340.
9. Camenisch G., 1996. Drug Transport Across Membranes: Structure-Property Correlations in the Prediction of Passive Membrane Permeation. Ph.D. Thesis, ETH Zürich, Switzerland.
10. Camenisch, G., Folkers, G., Van de Waterbeemd, H., 1996. Review of theoretical passive drug absorption models: Historical background, recent developments and limitations. Pharm. Acta Helv. 71, 309-327.
11. Camenisch, G., Folkers, G., Van de Waterbeemd, H., 1998. Shapes of membrane permeability-lipophilicity curves: Extension of theoretical models including an aqueous pore pathway. Eur. J. Pharm. Sci. 6, 321-329.
12. Camenisch, G., Folkers, G., Van de Waterbeemd, H., 1997. Comparision of passive drug transport through Caco-2 cells and artificial membranes. A simple method to estimate the absorption potential of new compounds. Int. J. Pharm. 147, 61-70.
13. Chan, O.H., Stewart, B.H., 1996. Physicochemical and drug-delivery considerations for oral drug bioavailability. Drug Discov. Today 1, 461-473.
14. Conradi R.A., Burton P.S., Borchardt R.T., 1996. Physicochemical and biological factors that influence a drug's cellular permeability by passive diffusion. In: Pliska V., Testa B., Van de Waterbeemd H. (Eds.), Lipophilicity in Drug Action and Toxicology. VCH, Weinheim, pp. 233-252.
15. El Tayar, N., Testa, B., Carrupt, P.A., 1992. Polar intermolecular interactions encoded in partition coefficients: An indirect estimation of hydrogen-bonding parameters of polyfunctional solutes. J. Phys. Chem. 96, 1455-1459.
16. He, Y.-L., Murby, S., Gifford, L., Collett, A., Warhurst, G., Douglas, K.T., Rowland, M., Ayrton, F., 1996. Oral absorption of D-oligopeptides in rats via the paracellular route. Pharm. Res. 13, 1673-1678.
17. Hilgers, A.R., Conradi, R.A., Burton, P.S., 1990. Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Pharm. Res. 7, 902-910.
18. Hillgren, K.M., Kato, A., Borchardt, R.T., 1995. In vitro systems for studying intestinal drug absorption. Med. Res. Revs. 15, 83-109.
19. Karlsson, J., Wikman, A., Artursson, P., 1993. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein. Br. J. Pharmacol. 110, 1009-1016.
20. Leahy D.E., Lynch J., Taylor D.C., 1989. Mechanisms of absorption of small molecules. In: Prescott L.F., Nimmo W.S. (Eds.), Novel Drug Delivery and its Therapeutic Application, John Wiley and Sons, New York, pp. 33-44.
21. Lennernäs, H., 1995. Does fluid flow across the intestinal mucosa affect quantitative oral drug absorption? Is it time for a reevaluation?. Pharm. Res. 12, 1573-1582.
22. Lieb, W.R., Stein, W.D., 1971. The molecular basis of simple diffusion within biological membranes. Curr. Top. Membr. Transp. 2, 1-39.
23. Palm, K., Luthman, K., Ungell, A.L., Strandlund, G., Artursson, P., 1996. Correlation of drug absorption with molecular surface properties. J. Pharm. Sci. 85, 32-39.
24. Palm, K., Stenberg, P., Luthman, K., Artursson, P., 1997. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 14, 568-571.
25. Pauletti G.M., Okumu F.W., Vander Velde D.G., Borchardt R.T., 1996. The effect of charge and conformational flexibility on the pathway of permeation of model hexapeptides across Caco-2 cell monolayers in unperturbed and perturbed states. Pharm Res. (Suppl.) 13, S-235.
26. Rose, V.S., Rahr, E., Hudson, B.D., 1994. The use of procrustes analysis to compare different property sets for the characterization of a diverse set of compounds. Quant. Struct.-Act. Relat. 13, 152-158.
27. Rubas, W., Cromwell, M., Gadek, T., Narindray, D., Mrsny, R., 1994. Structural elements which govern the resistance of intestinal tissues to compound transport. Mat. Res. Soc. Symp. Proc. 331, 179-185.
28. Stehle, R.G., Higuchi, W.I., 1972. In vitro model for transport of solutes in three-phase system I: Theoretical principles. J. Pharm. Sci. 61, 1922-1930.
29. Tamura, K., Lee, C.-P., Smith, P.L., Borchardt, R.T., 1996. Effect of charge on oligopeptide transporter-mediated permeation of cyclic dipeptides across Caco-2 cell monolayers. Pharm. Res. 13, 1752-1754.
30. Testa, B., Seiler, P., 1981. Steric and lipophilic components of the hydrophobic fragmental constant. Arzneim. Forsch. (Drug Res.) 31, 1053-1058.
31. Van de Waterbeemd, H., 1997. Application of physicochemical methods to oral drug absorption estimation. Eur. J. Pharm. Sci. 5 (Suppl. 2), S26-S27.
32. Van de Waterbeemd H., Camenisch G., Folkers G., Chrétien J.R., Raevsky, O.A. Estimation of blood-brain barrier penetration of drugs using molecular size, shape and H-bonding descriptors. J. Drug Traffic. in press.
33. Van de Waterbeemd, H., Camenisch, G., Folkers, G., Raevsky, O., 1996. Estimation of Caco-2 cell permeability using calculated molecular descriptors. Quant. Struct.-Act. Relat. 15, 480-490.
34. Wacher, V.J., Salphati, L., Benet, L.Z., 1996. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Revs. 20, 99-112.
35. Walter, A., Gutknecht, J., 1986. Permeability of small nonelectrolytes through lipid bilayer membranes. J. Membr. Biol. 90, 207-217.
36. Xiang, T.X., Anderson, B.D., 1994. The relationship between permeant size and permeability in lipid bilayer membranes. J. Membr. Biol. 140, 111-122.