Computational models to predict aqueous drug solubility, permeability and intestinal absorption

Expert Opinion on Drug Metabolism and Toxicology

Volumn 1, Issue 4, 2005, Pages 613-627

  Bergströöm, Christel A S ^a  

^a UPPSALA UNIVERSITY   (Sweden)

Author keywords

drug like; in silico; in vitro; intestinal absorption; molecular descriptors; multivariate data analysis; permeability; statistics

Indexed keywords

DRUG;

CHEMISTRY; INTESTINE ABSORPTION; MATHEMATICS; PERMEABILITY; REVIEW; SOLUBILITY; SOLUTION AND SOLUBILITY; THEORETICAL MODEL;

INTESTINAL ABSORPTION; MATHEMATICS; MODELS, THEORETICAL; PERMEABILITY; PHARMACEUTICAL PREPARATIONS; SOLUBILITY; SOLUTIONS;

EID: 33747116165     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.1.4.613     Document Type: Review

References (145)

1. KENNEDY T: Managing the drug discovery /development interface. Drug Discov. Today (1997) 2:436-444. (Pubitemid 27387353)
2. CLARK DE, GROOTENHUIS PD: Progress in computational methods for the prediction of ADMET properties. Curr. Opin. Drug Discov. Devel. (2002) 5(3):382-390. (Pubitemid 36285643)
3. MODI S: Computational approaches to the understanding of ADMET properties and problems. Drug Discov. Today (2003) 8(14):621-623. (Pubitemid 36809256)
4. VAN DE WATERBEEMD H, GIFFORD E: ADMET in silico modelling: towards prediction paradise? Nat. Rev. Drug Discov. (2003) 2(3):192-204. (Pubitemid 37361664)
5. 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(3):880-885.
6. ARTURSSON P, BORCHARDT RT: Intestinal drug absorption and metabolism in cell culture: Caco-2 and beyond. Pharm. Res. (1997) 14(12):1655-1658. (Pubitemid 28062907)
7. LIPINSKI CA, LOMBARDO F, DOMINY BW, FEENY PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. (1997) 23:3-25. (Pubitemid 27046991)
8. KOLA I, LANDIS J: Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov. (2004) 3(8):711-716.
9. CHIOU WL: The rate and extent of oral bioavailability versus the rate and extent of oral absorption: clarification and recommendation of terminology. J. Pharmacokinet. Biopharm. (2001) 28(1):3-6.
10. PAN L, HO Q, TSUTSUI K, TAKAHASHI L: Comparison of chromatographic and spectroscopic methods used to rank compounds for aqueous solubility. J. Pharm. Sci. (2001) 90(4):521-529.
11. TAUB ME, KRISTENSEN L, FROKJAER S: Optimized conditions for MDCK permeability and turbidimetric solubility studies using compounds representative of BCS classes I - IV. Eur. J. Pharm. Sci. (2002) 15(4):331-340. (Pubitemid 34436920)
12. BERGSTRÖM CAS, NORINDER U, LUTHMAN K, ARTURSSON P: Experimental and computational screening models for prediction of aqueous drug solubility. Pharm. Res. (2002) 19(2):182-188. (Pubitemid 34165404)
13. GLOMME A, MÄRZ J, DRESSMAN J: Comparison of a miniaturized shake-flask solubility method with automated potentiometric acid/base titrations and calculated solubilities. J. Pharm. Sci. (2005) 94(1):1-16. (Pubitemid 40116365)
14. PIDGEON C, ONG S, LIU H et al.: IAM chromatography: an in vitro screen for predicting drug membrane permeability. J. Med. Chem. (1995) 38:590-594.
15. ONG S, LIU H, PIDGEON C: Immobilized-artificial-membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability. J. Chromatogr. A (1996) 728(1-2):113-128. (Pubitemid 26146680)
16. 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. (1998) 41(7):1007-1010. (Pubitemid 28207375)
17. BERMEJO M, AVDEEF A, RUIZ A et al.: PAMPA-a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones. Eur. J. Pharm. Sci. (2004) 21(4):429-441. (Pubitemid 38283916)
18. 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(3):736-749. (Pubitemid 19057595)
19. ENGMAN HA, LENNERNÄS H, TAIPALENSUU J, OTTER C, LEIDVIK B, ARTURSSON P: CYP3A4, CYP3A5, and MDR1 in human small and large intestinal cell lines suitable for drug transport studies. J. Pharm. Sci. (2001) 90(11):1736-1751. (Pubitemid 33062594)
20. POLLI JW, WRING SA, HUMPHREYS JE et al.: Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther. (2001) 299(2):620-628. (Pubitemid 32979675)
21. TAVELIN S, MILOVIC V, OCKLIND G, OLSSON S, ARTURSSON P: A conditionally immortilized epithelial cell line for studies of intestinal drug transport. J. Pharmacol. Exp. Ther. (1999) 290(3):1212-1221. (Pubitemid 29400263)
22. TAVELIN S, TAIPALENSUU J, SODERBERG L, MORRISON R, CHONG S, ARTURSSON P: Prediction of the oral absorption of low-permeability drugs using small intestine-like 2/4/A1 cell monolayers. Pharm. Res. (2003) 20(3):397-405. (Pubitemid 36288368)
23. 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(1):28-33. (Pubitemid 29037364)
24. LENNERNÄS H, AHRENSTEDT Ö, HÄLLGREN R, KNUTSON L, RYDE M, PAALZOW L: Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. Pharm. Res. (1992) 9:1243-1251.
25. FAGERHOLM U, JOHANSSON M, LENNERNÄS H: Comparison between permeability coefficients in rats and human jejunum. Pharm. Res. (1996) 13:1336-1342. (Pubitemid 26344978)
26. LENNERNÄS H, NYLANDER S, UNGELL A-L: Jejunal permeability: a comparison between the ussing chamber technique and the single-pass perfusion in humans. Pharm. Res. (1997) 14:667-671. (Pubitemid 27220288)
27. UNGELL AL, NYLANDER S, BERGSTRAND S, SJÖBERG A, LENNERNÄS H: Membrane transport of drugs in different regions of the intestinal tract of the rat. J. Pharm. Sci. (1998) 87(3):360-366. (Pubitemid 28204591)
28. KIER LB, HALL LH: Connectivity in structure-activity analysis. Research Studies Press, John Wiley and Sons, Letchworth, UK (1986).
29. KIER LB, HALL LH: An electrotopological-state index for atoms in molecules. Pharm. Res. (1990) 7(8):801-807. (Pubitemid 20332531)
30. MANNHOLD R, REKKER RF, SONNTAG C, TER LAAK AM, DROSS K, POLYMEROPOULOS EE: Comparative evaluation of the predictive power of calculation procedures for molecular lipophilicity. J. Pharm. Sci. (1995) 84(12):1410-1419.
31. ABRAHAM MH: Scales of solute hydrogen-bonding: their construction and application to physicochemical and biochemical processed. Chem. Soc. Rev. (1993) 22:73-83.
32. MANNHOLD R, VAN DE WATERBEEMD H: Substructure and whole molecule approaches for calculating logP. J. Comput. Aided. Mol. Des. (2001) 15(4):337-354. (Pubitemid 32366724)
33. RAEVSKY OA, SKVORTSOV VS: 3D hydrogen bond thermodynamics (HYBOT) potentials in molecular modelling. J. Comput. Aided. Mol. Des. (2002) 16(1):1-10. (Pubitemid 34855040)
34. PALM K, STENBERG P, LUTHMAN K, ARTURSSON P: Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. (1997) 14(5):568-571. (Pubitemid 27220272)
35. STENBERG P, LUTHMAN K, ARTURSSON P: Prediction of membrane permeability to peptides from calculated dynamic molecular surface properties. Pharm. Res. (1999) 16(2):205-212. (Pubitemid 29135123)
36. STENBERG P, NORINDER U, LUTHMAN K, ARTURSSON P: Experimental and computational screening models for the prediction of intestinal drug absorption. J. Med. Chem. (2001) 44(12):1927-1937. (Pubitemid 32884517)
37. VAN DE WATERBEEMD H, KANSY M: Hydrogen-bonding capacity and brain penetration. Chimia (1992) 46:299-303.
38. WINIWARTER S, BONHAM NM, 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. (1998) 41(25):4939-4949. (Pubitemid 28555452)
39. ERTL P, ROHDE B, SELZER P: Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J. Med. Chem. (2000) 43(20):3714-3717.
40. CRUCIANI G, PASTOR M, GUBA W: VolSurf: a new tool for the pharmacokinetic optimization of lead compounds. Eur. J. Pharm. Sci. (2000) 11(Suppl. 2):S29-S39.
41. NORINDER U, ÖSTERBERG T, ARTURSSON P: Theoretical calculation and prediction of Caco-2 cell permeability using MolSurf parametrization and PLS statistics. Pharm. Res. (1997) 14(12):1786-1791. (Pubitemid 28062926)
42. 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. (1999) 8(1):49-56. (Pubitemid 29117268)
43. CLARK DE: Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration. J. Pharm. Sci. (1999) 88(8):815-821.
44. CLARK DE: Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J. Pharm. Sci. (1999) 88(8):807-814.
45. MOTULSKY H: Intuitive biostatistics. Oxford University Press, Inc., New York, US (1995).
46. HÖSKULDSSON A: PLS regression methods. J. Chemometr. (1988) 2:211-228.
47. OPREA TI, GOTTFRIES J: Toward minimalistic modeling of oral drug absorption. J. Mol. Graph. Model. (1999) 17(5-6):261-274.
48. ICHIKAWA H: Hierarchy neural networks as applied to pharmaceutical problems. Adv. Drug Deliv. Rev. (2003) 55(9):1119-1147. (Pubitemid 37087922)
49. WINKLER DA, BURDEN FR: Bayesian neural nets for modeling in drug discovery. Drug Discov. Today: Biosilico (2004) 2(3):104-111.
50. GOMBAR VK, POLLI JW, HUMPHREYS JE, WRING SA, SERABJIT-SINGH CS: Predicting Pglycoprotein substrates by a quantitative structure-activity relationship model. J. Pharm. Sci. (2004) 93(4):957-968. (Pubitemid 38420406)
51. BERGSTRÖM CAS, LUTHMAN K, ARTURSSON P: Accuracy of calculated pH-dependent aqueous drug solubility. Eur. J. Pharm. Sci. (2004) 22(5):387-398. (Pubitemid 38953897)
52. AJAY A, WALTERS WP, MURCKO MA: Can we learn to distinguish between druglike and nondrug-like molecules? J. Med. Chem. (1998) 41(18):3314-3324. (Pubitemid 28406538)
53. FRIMURER TM, BYWATER R, NAERUM L, LAURITSEN LN, BRUNAK S: Improving the odds in discriminating drug-like from non druglike compounds. J. Chem. Inf. Comput. Sci. (2000) 40(6):1315-1324.
54. OPREA TI: Property distribution of drugrelated chemical databases. J. Comput. Aided. Mol. Des. (2000) 14(3):251-264. (Pubitemid 30175944)
55. OPREA TI, GOTTFRIES J: Chemography: the art of navigating in chemical space. J. Comb. Chem. (2001) 3(2):157-166. (Pubitemid 33614499)
56. WALTERS WP, MURCKO MA: Prediction of drug-likeness. Adv. Drug Deliv. Rev. (2002) 54(3):255-271.
57. PICKETT SD, MCLAY IM, CLARK DE: Enhancing the hit-to-lead properties of lead optimization libraries. J. Chem. Inf. Comput. Sci. (2000) 40(2):263-272.
58. HILDEBRAND J: Solubility. XII. Regular solutions. J. Am. Chem. Soc. (1929) 51:66-80.
59. SCATCHARD G: Equilibria in nonelectrolyte solutions in relation to the vapor pressures and densities of the components. Chem. Rev. (1931) 8:321-333.
60. HILDEBRAND JC, SCOTT RL: The solubility of nonelectrolytes. Reinhold Publishing Corporation, New York, US (1950).
61. KAMLET MJ, ABBOUD J-LM, ABRAHAM MH, TAFT RW: Linear solvation energy relationships. 23. A comprehensive collection of the solvatochrominc parameters, ã, á and â, and some methods for simplifying the generalized solvatochromic equation. J. Org. Chem. (1983) 48:2877-2887.
62. KAMLET MJ, DOHERTY RM, ABBOUD J-LM, ABRAHAM MH, TAFT RW: Linear solvation energy relationships: 36. Molecular properties governing solubilities of organic nonelectrolytes in water. J. Pharm. Sci. (1986) 75(4):338-349. (Pubitemid 16137100)
63. BUSTAMANTE P, MARTIN A, GONZALEZ-GUISANDEZ MA: Partial solubility parameters and solvatochromic parameters for predicting the solubility of single and multiple drugs in individual solvents. J. Pharm. Sci. (1993) 82(6):635-640. (Pubitemid 23216011)
64. BUSTAMANTE P, ESCALERA B, MARTIN A, SELLES E: A modification of the extended Hildebrand approach to predict the solubility of structurally related drugs in solvent mixtures. J. Pharm. Pharmacol. (1993) 43:253-257. (Pubitemid 23123533)
65. KAMLET MJ, DOHERTY RM, FISEROVA-BERGEROVA V, CARR PW, ABRAHAM MH, TAFT RW: Solubility properties in biological media 9. Prediction of solubility and partition of organic nonelectrolytes in blood and tissue from solvatochromic parameters. J. Pharm. Sci. (1987) 76(1):14-17. (Pubitemid 17023044)
66. ABRAHAM MH, LE J: The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship. J. Pharm. Sci. (1999) 88(9):868-880. (Pubitemid 29438950)
67. HANSCH C, QUINLAN JE, LAWRENCE GL: The linear free-energy relationship between partition coefficients and the aqueous solubility of organic liquids. J. Org. Chem. (1968) 33(1):347-350.
68. YALKOWSKY SH, VALVANI SC: Solubility and partitioning I: solubility of nonelectrolytes in water. J. Pharm. Sci. (1980) 69(8):912-922. (Pubitemid 11234579)
69. YALKOWSKY SH: Solubility and partitioning V: dependence of solubility on melting point. J. Pharm. Sci. (1981) 70(8):971-973. (Pubitemid 11025600)
70. YALKOWSKY SH, PINAL R, BANERJEE S: Water solubility: a critique of the solvatochromic approach. J. Pharm. Sci. (1988) 77(1):74-77.
71. YALKOWSKY SH, PINAL R: Estimation of the aqueous solubility of complex organic componds. Chemosphere (1993) 26(7):1239-1261. (Pubitemid 23133145)
72. LI A, YALKOWSKY SH: Solubility of organic solutes in ethanol/water mixtures. J. Pharm. Sci. (1994) 83(12):1735-1740.
73. MYRDAL PB, MANKA AM, YALKOWSKY SH: Aquafac 3: aqueous functional group activity coefficients; application to the estimation of aqueous solubility. Chemosphere (1995) 30(9):1619-1637.
74. RAN Y, YALKOWSKY SH: Prediction of drug solubility by the general solubility equation (GSE). J. Chem. Inf. Comput. Sci. (2001) 41(2):354-357. (Pubitemid 32408650)
75. BERGSTRÖM CAS, NORINDER U, LUTHMAN K, ARTURSSON P: Molecular descriptors influencing melting point and their role in classification of solid drugs. J. Chem. Inf. Comput. Sci. (2003) 43(4):1177-1185.
76. CLARK M: Generalized fragmentsubstructure- based property prediction method. J. Chem. Inf. Model. (2005) 45(1):30-38. (Pubitemid 40736953)
77. KARTHIKEYAN M, GLEN RC, BENDER A: General melting point prediction based on a diverse compound data set and artificial neural networks. J. Chem. Inf. Model. (2005) 45(3):581-590. (Pubitemid 40795164)
78. MEYLAN WM, HOWARD PH, BOETHLING RS: Improved method for estimating water solubility from octanol/ water partition coefficient. Environ. Toxicol. Chem. (1996) 15(2):100-106. (Pubitemid 26055515)
79. MCFARLAND JW, AVDEEF A, BERGER CM, RAEVSKY OA: Estimating the water solubilities of crystalline compounds from their chemical structures alone. J. Chem. Inf. Comput. Sci. (2001) 41:1355-1359.
80. RAEVSKY OA, TREPALIN SV, TREPALINA HP, GERASIMENKO VA, RAEVSKAJA OE: SLIPPER-2001 - software for predicting molecular properties on the basis of physicochemical descriptors and structural similarity. J. Chem. Inf. Comput. Sci. (2002) 42(3):540-549. (Pubitemid 35355260)
81. AMIDON GL, YALKOWSKY SH, LEUNG S: Solubility of nonelectrolytes in polar solvents II. Solubility of aliphatic alcohols in water. J. Pharm. Sci. (1974) 63(12):1866.
82. JORGENSEN WL, DUFFY EM: Prediction of drug solubility from structure. Adv. Drug Deliv. Rev. (2002) 54(3):355-366. (Pubitemid 34260958)
83. MITCHELL BE, JURS PC: Prediction of aqueous solubility of organic compounds from molecular structure. J. Chem. Inf. Comput. Sci. (1998) 38(3):489-496. (Pubitemid 128594464)
84. WANCHANA S, YAMASHITA F, HASHIDA M: Quantitative structure/ property relationship analysis on aqueous solubility using genetic algorithm-combined partial least squares method. Pharmazie (2002) 57(2):127-129. (Pubitemid 34151530)
85. CATANA C, GAO H, ORRENIUS C, STOUTEN PF: Linear and nonlinear methods in modeling the aqueous solubility of organic compounds. J. Chem. Inf. Model. (2005) 45(1):170-176. (Pubitemid 40736969)
86. BODOR N, HUANG M-J: A new method for the estimation of the aqueous solubility of organic compounds. J. Pharm. Sci. (1992) 81(9):954-960. (Pubitemid 23006854)
87. NELSON TM, JURS PC: Prediction of aqueous solubility of organic compounds. J. Chem. Inf. Comput. Sci. (1993) 34(3):601-609.
88. SUTTER JM, JURS PC: Prediction of aqueous solubility for a diverse set of heteroatom-containing organic compounds using a quantitative structure-property relationship. J. Chem. Inf. Comput. Sci. (1996) 36:100-107. (Pubitemid 126579140)
89. HUUSKONEN J, SALO M, TASKINEN J: Neural network modeling for estimation of the aqueous solubility of structurally related drugs. J. Pharm. Sci. (1997) 86(4):450-454. (Pubitemid 27154760)
90. HUUSKONEN J, SALO M, TASKINEN J: Aqueous solubility prediction of drugs based on molecular topology and neural network modeling. J. Chem. Inf. Comput. Sci. (1998) 38:450-456. (Pubitemid 128594458)
91. HUUSKONEN J, RANTANEN J, LIVINGSTONE D: Prediction of aqueous solubility for a diverse set of organic compounds based on atom-type electrotopological state indices. Eur. J. Med. Chem. (2000) 35(12):1081-1088. (Pubitemid 32050014)
92. HUUSKONEN J: Estimation of aqueous solubility for a diverse set of organic compounds based on molecular topology. J. Chem. Inf. Comput. Sci. (2000) 40(3):773-777.
93. HUUSKONEN J: Estimation of water solubility from atom-type electrotopological state indices. Environ. Toxicol. Chem. (2001) 20(3):491-497. (Pubitemid 32861530)
94. HUUSKONEN J: Estimation of aqueous solubility in drug design. Comb. Chem. High Throughput Screen. (2001) 4(3):311-316. (Pubitemid 32433642)
95. YAFFE D, COHEN Y, ESPINOSA G, ARENAS A, GIRALT F: A fuzzy ARTMAP based on quantitative structure-property relationships (QSPRs) for predicting aqueous solubility of organic compounds. J. Chem. Inf. Comput. Sci. (2001) 41(5):1177-1207.
96. TETKO IV, TANCHUK VY, KASHEVA TN, VILLA AE: Estimation of aqueous solubility of chemical compounds using E-state indices. J. Chem. Inf. Comput. Sci. (2001) 41(6):1488-1493.
97. ENGKVIST O, WREDE P: Highthroughput, in silico prediction of aqueous solubility based on one- and twodimensional descriptors. J. Chem. Inf. Comput. Sci. (2002) 42(5):1247-1249. (Pubitemid 35360309)
98. CHENG A, MERZ KM: Prediction of aqueous solubility of a diverse set of compounds using quantitative structure- property relationships. J. Med. Chem. (2003) 46:3572-3580. (Pubitemid 36988646)
99. VOTANO JR, PARHAM M, HALL LH, KIER LB: New predictors for several ADME/Tox properties: aqueous solubility, human oral absorption, and Ames genotoxicity using topological descriptors. Mol. Div. (2004) 8(4):379-391. (Pubitemid 39491373)
100. BERGSTRÖM CAS, STRAFFORD M, LAZOROVA L, AVDEEF A, LUTHMAN K, ARTURSSON P: Absorption classification of oral drugs based on molecular surface properties. J. Med. Chem. (2003) 46(4):558-570. (Pubitemid 36182757)
101. BERGSTRÖM CAS, WASSVIK CM, NORINDER U, LUTHMAN K, ARTURSSON P: Global and local computational models for prediction of aqueous solubility of drug-like molecules. J. Chem. Inf. Comput. Sci. (2004) 44(4):1477-1488.
102. CONRADI RA, HILGERS AR, HO NF, BURTON PS: The influence of peptide structure on transport across Caco-2 cells. Pharm. Res. (1991) 8(12):1453-1460.
103. CONRADI RA, HILGERS AR, HO NF, BURTON PS: The influence of peptide structure on transport across Caco-2 cells. II. Peptide bond modification which results in improved permeability. Pharm. Res. (1992) 9(3):435-439.
104. REN S, DAS A, LIEN EJ: QSAR analysis of membrane permeability to organic compounds. J. Drug Target. (1996) 4:103-107. (Pubitemid 26381472)
105. PALM K, LUTHMAN K, UNGELL AL et al.: Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors. J. Med. Chem. (1998) 41(27):5382-5392. (Pubitemid 29031322)
106. CAMENISCH G, ALSENZ J, VAN DE WATERBEEMD H, FOLKERS G: Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs lipophilicity and molecular weight. Eur. J. Pharm. Sci. (1998) 6(4):317-324.
107. HJORTH KRARUP L, THOGER CHRISTENSEN I, HOVGAARD L, FROKJAER S: Predicting drug absorption from molecular surface properties based on molecular dynamics simulations. Pharm. Res. (1998) 15(7):972-978. (Pubitemid 28356909)
108. VAN DE WATERBEEMD H, CAMENISCH G, FOLKERS G, CHRETIEN JR, RAEVSKY OA: Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J. Drug Target. (1998) 6(2):151-165. (Pubitemid 29033982)
109. ÖSTERBERG T, NORINDER U: Prediction of drug transport processes using simple parameters and PLS statistics. The use of ACD/logP and ACD/ChemSketch descriptors Eur. J. Pharm. Sci. 2001 12 3 327-337.
110. YAMASHITA F, WANCHANA S, HASHIDA M: Quantitative structure/ property relationship analysis of Caco-2 permeability using a genetic algorithmbased partial least squares method. J. Pharm. Sci. (2002) 91(10):2230-2239.
111. MARRERO PONCE Y, CABRERA PEREZ MA, ROMERO ZALDIVAR V, GONZALEZ DIAZ H, TORRENS F: A new topological descriptors based model for predicting intestinal epithelial transport of drugs in Caco-2 cell culture. J. Pharm. Pharm. Sci. (2004) 7(2):186-199. (Pubitemid 41528891)
112. STENBERG P, LUTHMAN K, ELLENS H et al.: Prediction of the intestinal absorption of endothelin receptor antagonists using three theoretical methods of increasing complexity. Pharm. Res. (1999) 16(10):1520-1526. (Pubitemid 29510547)
113. ZHAO YH, LE J, ABRAHAM MH et al.: Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J. Pharm. Sci. (2001) 90(6):749-784. (Pubitemid 32530451)
114. AGATONOVIC-KUSTRIN S, BERESFORD R, YUSOF AP: Theoretically-derived molecular descriptors important in human intestinal absorption. J. Pharm. Biomed. Anal. (2001) 25(2):227-237. (Pubitemid 32244232)
115. KLOPMAN G, STEFAN LR, SAIAKHOV RD: ADME evaluation: 2. A computer model for the prediction of intestinal absorption in humans. Eur. J. Pharm. Sci. (2002) 17(4-5):253-263. (Pubitemid 35365929)
116. NIWA T: Using general regression and probabilistic neural networks to predict human intestinal absorption with topological descriptors derived from twodimensional chemical structures. J. Chem. Inf. Comput. Sci. (2003) 43(1):113-119.
117. WOLOHAN PR, CLARK RD: Predicting drug pharmacokinetic properties using molecular interaction fields and SIMCA. J. Comput. Aided. Mol. Des. (2003) 17(1):65-76. (Pubitemid 36939541)
118. PEREZ MA, SANZ MB, TORRES LR, AVALOS RG, GONZALEZ MP, DIAZ HG: A topological sub-structural approach for predicting human intestinal absorption of drugs. Eur. J. Med. Chem. (2004) 39(11):905-916. (Pubitemid 39389100)
119. SUN H: A universal molecular descriptor system for prediction of logP, logS, logBB and absorption. J. Chem. Inf. Comput. Sci. (2004) 44(2):748-757.
120. XUE Y, LI ZR, YAP CW, SUN LZ, CHEN X, CHEN YZ: Effect of molecular descriptor feature selection in support vector machine classification of pharmacokinetic and toxicological properties of chemical agents. J. Chem. Inf. Comput. Sci. (2004) 44(5):1630-1638.
121. OBATA K, SUGANO K, SAITOH R et al.: Prediction of oral drug absorption in humans by theoretical passive absorption model. Int. J. Pharm. (2005) 293(1-2):183-192. (Pubitemid 40385116)
122. MATSSON P, BERGSTRÖM CAS, NAGAHARA N, TAVELIN S, NORINDER U, ARTURSSON P: Exploring the role of different drug transport routes in permeability screening. J. Med. Chem. (2005) 48(2):604-613. (Pubitemid 40139802)
123. CLARK RD, WOLOHAN PR: Molecular design and bioavailability. Curr. Top. Med. Chem. (2003) 3(11):1269-1288.
124. TURNER JV, MADDALENA DJ, AGATONOVIC-KUSTRIN S: Bioavailability prediction based on molecular structure for a diverse series of drugs. Pharm. Res. (2004) 21(1):68-82. (Pubitemid 38122294)
125. PARROTT N, LAVE T: Prediction of intestinal absorption: comparative assessment of GASTROPLUS and IDEA. Eur. J. Pharm. Sci. (2002) 17(1-2):51-61. (Pubitemid 35287171)
126. AMIDON GL, LENNERNÄS H, SHAH VP, CRISON JR: A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution an in vivo bioavailability. Pharm. Res. (1995) 12(3):413-420.
127. VARMA M, KHANDAVILLI S, ASHOKRAJ Y et al.: Biopharmaceutic classification system: a scientific framework for pharmacokinetic optimization in drug research. Curr. Drug Met. (2004) 5(5):375-388. (Pubitemid 39276602)
128. KASIM NA, WHITEHOUSE M, RAMACHANDRAN C et al.: Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol. Pharm. (2004) 1:85-96.
129. WU CY, BENET LZ: Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res. (2005) 22(1):11-23. (Pubitemid 40558141)
130. LIPINSKI CA: Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods (2000) 44(1):235-249. (Pubitemid 32239479)
131. http://www.fda.gov/cder/guidance/ index.htm Guidance for Industry. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system (2000).
132. http://www.daylight.com/smiles/ f-smiles.html SMILES (2005).
133. http://ap-algorithms.com Absolv is now a part of ADME boxes (2005).
134. http://software.timtec.net/slipper.htm SLIPPER (2005).
135. http://www.schrodinger.com/ ProductDescription.php?mID=6&sID= 10&cID=0 QikProp (2005).
136. http://www.acdlabs.com/products/ phys-chem-lab/aqsol/
137. http://ap-algorithms.com/ admet-probes.htm
138. http://ap-algorithms.com/adme-boxes.htm
139. http://ap-algorithms.com/ admetox-web.htm
140. http://www.simulations-plus.com/products/predictor.html
141. http://www.accelrys.com/products/datasheets/c2-adme-us-data.pdf
142. http://www.simulations-plus.com/products/gastro-plus.html
143. http://www.lionbioscience.com/solutions/nl/e19298/e19233/index-eng.html
144. http://www.bio-rad.com
145. http://www.bayertechnology.com/index2.htm