Virtual screening of intestinal drug permeability

Journal of Controlled Release

Volumn 65, Issue 1-2, 2000, Pages 231-243

  Stenberg, Patric ^a   Luthman, Kristina ^b   Artursson, Per ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b UNIVERSITY OF TROMSØ   (Norway)

Author keywords

Drug transport; Hydrogen bonding; Intestinal drug absorption; Lipophilicity; Polar molecular surface area

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; ENDOTHELIN RECEPTOR ANTAGONIST; PRODRUG;

ACTIVE TRANSPORT; ARTICLE; CELL STRAIN CACO 2; DRUG PENETRATION; DRUG RESEARCH; DRUG SCREENING; DRUG SOLUBILITY; HUMAN; HUMAN CELL; HYDROGEN BOND; INTESTINE ABSORPTION; LIPOPHILICITY; PASSIVE TRANSPORT; PRIORITY JOURNAL;

ANIMALS; BIOLOGICAL TRANSPORT; BIOPHARMACEUTICS; COMPUTER SIMULATION; DRUG DESIGN; HUMANS; INTESTINAL ABSORPTION; MODELS, BIOLOGICAL;

EID: 0034002854     PISSN: 01683659     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0168-3659(99)00239-4     Document Type: Article

References (93)

1. Lipinski C.A., Lombardo F., Dominy B.W., Feeney P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23:1997;3-25.
2. Testa B., Caldwell J. Prodrugs revisited: The "Ad Hoc" approach as a complement to ligand design. Med. Res. Rev. 16:1996;233-241.
3. Artursson P., Borchardt R.T. Intestinal drug absorption and metabolism in cell cultures: Caco-2 and beyond. Pharm. Res. 14:1997;1655-1658.
4. Garberg P., Eriksson P., Schipper N., Sjöström B. Automated absorption assessment using Caco-2 cells cultured on both sides of polycarbonate membranes. Pharm. Res. 16:1999;441-445.
5. Morrison R.A. Automation, reliability and limitations of Caco-2 intestinal permeability screening for selection of well-absorbed drug candidates, Early ADME and toxicology in drug discovery. IBC Conferences, Berkeley, CA, USA :1998.
6. Stevenson C.L., Augustijns P.F., Hendren R.W. Use of Caco-2 cells and LC/MS/MS to screen a peptide combinatorial library for permeable structures. Int. J. Pharm. 177:1999;103-115.
7. Lennernäs H., Palm K., Fagerholm U., Artursson P. Correlation between paracellular and transcellular drug permeability in the human jejunum and Caco-2 monolayers. Int. J. Pharm. 127:1996;103-107.
8. Chong S., Dando S.A., Soucek K.M., Morrison R.M. In vitro permeability through Caco-2 cells is not quantitatively predictive of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system. Pharm. Res. 13:1996;120-123.
9. Kansy M., Senner F., Gubernator K. Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes. J. Med. Chem. 41:1998;1007-1010.
10. Lundahl P., Beigi F. Immobilized liposome chromatography of drugs for model analysis of drug-membrane interactions. Adv. Drug Deliv. Rev. 23:1997;221-227.
11. Yang C.Y., Cai S.J., Liu H., Pidgeon C. Immobilized Artificial Membranes-screens for drug membrane interactions. Adv. Drug Deliv. Rev. 23:1997;229-256.
12. Palm K., Luthman K., Ungell A.-L., Strandlund G., Beigi F., Lundahl P., Artursson P. Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors. J. Med. Chem. 41:1998;5382-5392.
13. Beigi F., Gottschalk I., Lagerquist Hägglund C., Haneskog L., Brekkan E., Zhang Y., Österberg T., Lundahl P. Immobilized liposome and biomembrane partitioning chromatography of drugs for prediction of drug transport. Int. J. Pharm. 164:1998;129-137.
14. Martin Y.C. A practioner's perspective of the role of quantitative structure-activity analysis in medicinal chemistry. J. Med. Chem. 24:1981;229-237.
15. Burton P.S., Conradi R.A., Hilgers A.R., Ho N.N.F., Maggiora L.L. The relationship between peptide structure and transport across epithelial cell monolayers. J. Contr. Rel. 19:1992;87-98.
16. Kim D.-C., Burton P.S., Borchardt R.T. A correlation between the permeability characteristics of a series of peptides using an in vitro cell culture model (Caco-2) and those using an in situ perfused rat ileum model of the intestinal mucosa. Pharm. Res. 10:1993;1710-1714.
17. Lane M.E., O'Driscoll C.M., Corrigan O.I. The relationship between rat intestinal permeability and hydrophilic probe size. Pharm. Res. 13:1996;1554-1558.
18. Wang J., Schaner M.E., Thomassen S., Su S.F., Piquette-Miller M., Giacomini K.M. Functional and molecular characteristics of Na(+)-dependent nucleoside transporters. Pharm. Res. 14:1997;1524-1532.
19. Tsuji A., Tamai I. Carrier-mediated intestinal transport of drugs. Pharm. Res. 13:1996;963-977.
20. Nezu J., Tamai I., Oku A., Ohashi R., Yabuuchi H., Hashimoto N., Nikaido H., Sai Y., Koizumi A., Shoji Y., Takada G., Matsuishi T., Yoshino M., Kato H., Ohura T., Tsujimoto G., Hayakawa J., Shimane M., Tsuji A. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. NATURE Genet. 21:1999;91-94.
21. Sparreboom A., van Asperen J., Mayer U., Schinkel A.H., Smit J.W., Meijer D.K., Borst P., Nooijen W.J., Beijnen J.H., van Tellingen O. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. U.S.A. 94:1997;2031-2035.
22. 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. 175:1991;880-885.
23. Takanaga H., Tamai I., Tsuji A. pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells. J. Pharm. Pharmacol. 46:1994;567-570.
24. Karlsson J., Kuo S.-M., Ziemniak J., Artursson P. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: secretion mediated by multiple transporters including P-glycoprotein. Br. J. Pharmacol. 110:1993;1009-1016.
25. Sinko P.J., Balimane P.V. Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats. Biopharm. Drug Dispos. 19:1998;209-217.
26. Makhey V.D., Guo A., Norris D.A., Hu P., Yan J., Sinko P.J. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells. Pharm. Res. 15:1998;1160-1167.
27. Hunter J., Hirst B.H., Simmons N.L. Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. Res. 10:1993;743-749.
28. Saitoh H., Aungst B.J. Possible involvement of multiple P-glycoprotein-mediated efflux systems in the transport of verapamil and other organic cations across rat intestine. Pharm. Res. 12:1995;1304-1310.
29. Sandström R., Karlsson A., Knutson L., Lennernäs H. Jejunal absorption and metabolism of R/S-verapamil in humans. Pharm. Res. 15:1998;856-862.
30. Anderle P., Niederer E., Rubas W., Hilgendorf C., Spahn-Langguth H., Wunderli-Allenspach H., Merkle H.P., Langguth P. 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. 87:1998;757-762.
31. Schwarz U.I., Gramatte T., Krappweis J., Berndt A., Oertel R., von Richter O., Kirch W. Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans. Clin. Pharmacol. Ther. 65:1999;283-290.
32. Wacher V.J., Silverman J.A., Zhang Y., Benet L.Z. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm. Sci. 87:1998;1322-1330.
33. Sjövall J., Alvan G., Westerlund D. Oral cyclacillin interacts with the absorption of oral ampicillin, amoxycillin, and bacampicillin. Eur. J. Clin. Pharmacol. 29:1985;495-502.
34. Lennernäs H., Nilsson D., Aquilonius S.-M., Ahrenstedt Ö., Knutson L., Paalzow L.K. The effect of L-leucin on the absorption of levodopa, studied by regional jejeunal perfusion in man. Br. J. Clin. Pharmacol. 35:1993;243-250.
35. Lown K.S., Mayo R.R., Leichtman A.B., Hsiao H.L., Turgeon D.K., Schmiedlin-Ren P., Brown M.B., Guo W., Rossi S.J., Benet L.Z., Watkins P.B. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin. Pharmacol. Ther. 62:1997;248-260.
36. Nilsson D., Hansson L.E., Johansson K., Nyström C., Paalzow L., Aquilonius S.M. Long-term intraduodenal infusion of a water based levodopa-carbidopa dispersion in very advanced Parkinson's disease. Acta Neurol. Scand. 97:1998;175-183.
37. Pappenheimer J.R., Reiss K.Z. Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J. Membr. Biol. 100:1987;123-136.
38. Lennernäs H. Does fluid flow across the intestinal mucosa affect quantitative oral drug absorption? Is there time for reevaluation? Pharm. Res. 12:1995;1573-1582.
39. Gan L.S., Yanni S., Thakker D.R. Modulation of the tight junctions of the Caco-2 cell monolayers by H2-antagonists. Pharm. Res. 15:1998;53-57.
40. Pade V., Stavchansky S. Estimation of the relative contribution of the transcellular and paracellular pathway to the transport of passively absorbed drugs in the Caco-2 cell culture model. Pharm. Res. 14:1997;1210-1215.
41. Palm K., Ros J., Gråsjö J., Luthman K., Artursson P. Effect of molecular charge on intestinal epithelial drug transport. J. Pharmacol. Exp. Ther. 291:1999;435-443.
42. Aungst B.J., Saitoh H. Intestinal absorption barriers and transport mechanisms, including secretory transport, for a cyclic peptide, fibrinogen antagonist. Pharm. Res. 13:1996;114-119.
43. Ellens H., Eddy E.P., Lee C.-P., Dougherty P., Largo A., Xiang J.-N., Elliott J.D., Cheng H.-Y., Ohlstein E., Smith P.L. In vitro permeability screening for identification of orally bioavailable endothelin receptor antagonists. Adv. Drug Deliv. Rev. 23:1997;99-109.
44. Duizer E., Penninks A.H., Stenhuis W.H., Groten J.P. Comparison of permeability characteristics of the human colonic Caco-2 and rat small intestinal IEC-18 cell lines. J. Contr. Rel. 49:1997;39-49.
45. Paul E.C.A., Hochman J., Quaroni A. Conditionally immortalized intestinal epithelial cells: novel approach for study of differentiated enterocytes. Am. J. Physiol. 265:1993;C266-C278.
46. Tavelin S., Milovic V., Ocklind G., Olsson S., Artursson P. A conditionally immortalized epithelial cell line for studies of intestinal drug transport. J. Pharmacol. Exp. Ther. 290:1999;1222-1229.
47. Stein W.D. The Molecular Basis of Diffusion Across Cell Membranes. 1967;Academic Press Inc, New York.
48. Diamond J.M., Wright E.M. Molecular forces governing non-electrolyte permeation through cell membranes. Proc. R. Soc. Lond. B. 172:1969;273-316.
49. Hansch C., Steward A.R., Iwasa J. The correlation of localization rates of benzeneboronic acids in brain and tumor tissue with substituent constants. Mol. Pharmacol. 1:1965;87-92.
50. Yazdanian M., Glynn S.L., Wright J.L., Hawi A. Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds. Pharm. Res. 15:1998;1490-1494.
51. Collander R. The permeability of Nitella cells to non-electrolytes. Physiol. Plant. 7:1954;420-445.
52. Stein W.D. Transport and Diffusion Across Cell Membranes. 1986;Academic Press Inc, Orlando.
53. Buur A., Trier L., Magnusson C., Artursson P. Permeability of 5-fluorouracil and prodrugs in Caco-2 cell monolayers. Int. J. Pharm. 129:1996;223-231.
54. Ranaldi G., Seneci P., Guba W., Islam K., Sambuy Y. Transport of the antibacterial agent oxazolidin-2-one and derivatives across intestinal (Caco-2) and renal (MDCK) epithelial cell lines. Antimicrob. Agents Chemother. 40:1996;652-658.
55. Palm K., Luthman K., Ungell A.-L., Strandlund G., Artursson P. Correlation of drug absorption with molecular surface properties. J. Pharm. Sci. 85:1996;32-39.
56. Leo A., Jow P.Y.C., Silipo C., Hansch C. Calculation of hydrophobic constant (log P) from π and f constants. J. Med. Chem. 18:1975;865-868.
57. Rekker R.F. The Hydrophobic Fragmental Constant. 1977;Elsevier Scientific Publishing Company, Amsterdam.
58. Testa B., Carrupt P.-A., Gaillard P., Billois F., Weber P. Lipophilicty in molecular modeling. Pharm. Res. 13:1996;335-343.
59. Audry E. A new approach to structure-activity relations: the molecular lipophilicity potential. Eur. J. Med. Chem. 21:1986;71-72.
60. Mannhold R., Rekker R.F., Sonntag C., ter Laak A.M., Dross K., Polymeropoulos E.E. Comparative evaluation of the predictive power of calculation procedures for molecular lipophilicity. J. Pharm. Sci. 84:1995;1410-1419.
61. Van De Waterbeemd H., Mannhold R. Programs and methods for calculation of log P-values. Quantitative Structure-Activity Relationships. 15:1996;410-412.
62. Buchwald P., Bodor N. Octanol-water partition: searching for predictive models. Curr. Med. Chem. 5:1998;353-380.
63. Marrink S.J., Berendsen H.J.C. Simulation of water transport through a lipid membrane. J. Phys. Chem. 98:1994;4155-4168.
64. Jacobs R.E., White S.E. The nature of the hydrophobic binding of small peptides at the bilayer interfaces: implications for the insertion of transbilayer helices. Biochemistry. 28:1989;3421-3437.
65. Tieleman D.P., Marrink S.J., Berendsen H.J.C. A computer perspective of membranes: molecular dynamics studies of lipid bilayer systems. Biochim. Biophys. Acta. 1331:1997;235-270.
66. Burton P.S., Conradi R.A., Hilgers A.R. Transcellular mechanisms of peptide and protein absorption: passive aspects. Adv. Drug Deliv. Rev. 7:1991;365-386.
67. Stenberg P., Luthman K., Artursson P. Prediction of membrane permeability to peptides from calculated dynamic molecular surface properties. Pharm. Res. 16:1999;205-212.
68. Seiler P. Interconversion of lipophilicities from hydrocarbon/water systems into octanol/water system. Eur. J. Med. Chem. 9:1974;473-479.
69. El Tayar N., Testa B., Carrupt P.-A. Polar intermolecular interactions encoded in partition coefficients: an indirect estimation of hydrogen-bond parameters of polyfunctional solutes. J. Phys. Chem. 96:1992;1455-1459.
70. Chikhale E.G., Ng K.-Y., Burton P.S., Borchardt R.T. Hydrogen bonding potential as a determinant of the in vitro and in vivo blood-brain barrier permeability of peptides. Pharm. Res. 11:1994;412-419.
71. 2 receptor histamine antagonists. J. Med. Chem. 31:1988;656-671.
72. Conradi R.A., Hilgers A.R., Vidmar T.J., Burton P.S. A non-aqueous partitioning system for predicting the oral absorption potential of peptides. Quant. Struct.-Act. Relat. 13:1994;4-10.
73. Goodwin J.T., Burton P.S., Hilgers A.R., Conradi R.A., Ho N.N.F. Relationships between physicochemical properties for a series of peptides and membrane permeability in Caco-2 cells. Pharm. Res. 13:1996;S243.
74. Ren S., Das A., Lien E.L. QSAR analysis of membrane permeability to organic compounds. J. Drug Target. 4:1996;103-107.
75. Palm K., Stenberg P., Luthman K., Artursson P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 14:1997;568-571.
76. Raevsky O.A., Grigor'ev V.Y., Kireev D.B., Zefirov N.S. Complete thermodynamic description of H-bonding in the framework of multiplicative approach. Quant. Struct.-Act. Relat. 11:1992;49-63.
77. Norinder U., Svensson P. Descriptors for amino acids using MolSurf parametrization. J. Comp. Chem. 19:1998;51-59.
78. van de Waterbeemd H., Camenisch G., Folkers G., Raevsky O.A. Estimation of Caco-2 cell permeability using calculated molecular descriptors. Quant. Struct.-Act. Relat. 15:1996;480-490.
79. Norinder U., Österberg T., Artursson P. Theoretical calulation and prediction of Caco-2 cell permeability using MolSurf parametrization and PLS statistics. Pharm. Res. 14:1997;1785-1790.
80. Norinder U., Österberg T., Artursson P. Theoretical calculation and prediction of intestinal absorption of drugs in humans using MolSurf parametrization and PLS statistics. Eur. J. Pharm. Sci. 8:1999;49-56.
81. Stenberg P., Luthman K., Ellens H., Lee C.-P., Smith P.L., Lago A., Elliott J.D., Artursson P. Prediction of the intestinal absorption of endothelin receptor antagonists using three theoretical methods of increasing complexity. Pharm. Res. 16:1999;1520-1526.
82. Barlow D., Satoh T. The design of peptide analogues for improved absorption. J. Contr. Rel. 29:1994;283-291.
83. Ooi T., Oobatake M., Némethy G., Scheraga H.A. Acessible surface areas as a measure of the thermodynamic parameters of hydration of peptides. Proc. Natl. Acad. Sci. USA. 84:1987;3086-3090.
84. Amidon G.L., Yalkowsky S.H., Anik S.T., Valvani S.C. Solubility of nonelectrolytes in polar solvents. V. Estimation of the solubililty of aliphatic monofunctional compounds in water using a molecular surface area approach. J. Phys. Chem. 79:1975;2239-2246.
85. van de Waterbeemd H., Kansy M. Hydrogen-bonding capacity and brain penetration. Chimia. 46:1992;299-303.
86. Krarup L.H., Christensen I.T., Hovgaard L., Frokjaer S. Predicting drug absorption from molecular surface properties based on molecular dynamics simulations. Pharm. Res. 15:1998;972-978.
87. Winiwarter S., Bonham N.M., Ax F., Hallberg A., Lennernäs H., Karlen A. Correlation of human jejunal permeability (in vivo) of drugs with experimentally and theoretically derived parameters. A multivariate data analysis approach. J. Med. Chem. 41:1998;4939-4949.
88. MAREA v1.4, The program MAREA is available upon request from the authors. The program is provided free of charge for academic users. Contact Johan Gråsjö (email: johan.grasjo@galenik.uu.se).
89. MolSurf v3.11, Qemist AB, Hertig Carls Allé 29, SE-691 41 Karlskoga, Sweden. http://members.xoom.com/Qemist.
90. Höskuldsson A. PLS regression methods. J. Chemometrics. 2:1988;211-228.
91. Gröning R., Braun F.J. Three-dimensional solubility parameters and their use in characterising the permeation of drugs through the skin. Pharmazie. 51:1996;337-341.
92. Breitkreutz J. Prediction of intestinal drug absorption properties by three-dimensional solubility parameters. Pharm. Res. 15:1998;1370-1375.
93. Wessel M.D., Jurs P.C., Tolan J.W., Muskal S.M. Prediction of human intestinal absorption of drug compounds from molecular structure. J. Chem. Inf. Comput. Sci. 38:1998;726-735.