Prediction of drug absorption using multivariate statistics

Journal of Medicinal Chemistry

Volumn 43, Issue 21, 2000, Pages 3867-3877

  Egan, W J ^a   Merz Jr , K M ^a   Baldwin, J J ^a  

^a PHARMACOPEIA INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG;

ANIMAL CELL; ARTICLE; CELL STRAIN CACO 2; DRUG ABSORPTION; MOLECULAR WEIGHT; MULTIVARIATE ANALYSIS; NONHUMAN; PREDICTION; STATISTICAL MODEL;

BIOLOGICAL TRANSPORT; CACO-2 CELLS; CELL MEMBRANE PERMEABILITY; HUMANS; INTESTINAL ABSORPTION; MODELS, BIOLOGICAL; MULTIVARIATE ANALYSIS; PHARMACEUTICAL PREPARATIONS; REPRODUCIBILITY OF RESULTS;

EID: 0034687231     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000292e     Document Type: Article

References (98)

1. Pharma 2005-An industrial revolution in R and D
2. Rising costs hold up drug discovery
3. Drug selection in early drug development: Screening for acceptable pharmacokinetic properties using combined in vitro and computational approaches
4. Success rate for new drugs entering clinical testing in the United States
5. An introduction to drug disposition: The basic principles of absorption, distribution, metabolism, and excretion
6. Role of pharmacokinetics and metabolism in drug discovery and development
7. Pharmacokinetics and metabolism in early drug discovery
8. E pluribus product
9. Selecting leads with pharmacokinetic data
10. Preclinical drug metabolism in the age of high-throughput screening: An industrial perspective
11. Approaches to higher-throughput pharmacokinetics (HTPK) in drug discovery
12. ADME/PK assays in screening for orally active drug candidates
13. High-throughput approaches for evaluating absorption, distribution, metabolism, and excretion properties of lead compounds
14. Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics
15. Compound optimization in early- and late-phase drug discovery: Acceptable pharmacokinetic properties utilizing combined physicochemical, in vitro, and in vivo screens
16. Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964-1985)
17. Computational methods for the prediction of 'drug-likeness'
18. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
19. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases
20. Polar molecular surface properties predict the intestinal absorption of drugs in humans
21. Evaluation of dynamic polar molecular surface area as predictor of drug absorption: Comparison with other computational and experimental predictors
22. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption
23. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs
24. Prediction of membrane permeability to peptides from calculated dynamic molecular surface properties
25. Estimation of permeability by passive diffusion through Caco-2 cell monolayers using drugs' lipophilicity and molecular weight
26. Shape of membrane permeability-lipophilicity curves: Extension of theoretical models with an aqueous pore pathway
27. Estimation of Caco-2 cell permeability using calculated molecular descriptors
28. Theoretical calculation and prediction of Caco-2 cell permeability using molsurf parametrization and PLS statistics
29. Theoretical calculation and prediction of intestinal absorption of drugs in humans using molsurf parametrization and PLS statistics
30. Prediction of human intestinal absorption of drug compounds from molecular structure
31. Correlation of human jejunal permeability (in vivo) of drugs with experimentally and theoretically derived parameters. A multivariate data analysis approach
32. Structure-property model for membrane partitioning of oligopeptides
33. Enhancing the hit-to-lead properties of lead optimization libraries
34. Physicochemical and drug-delivery considerations for oral drug bioavailability
35. Design principles for orally bioavailable drugs
36. Physicochemical and biological factors that influence a drug's cellular permeability by passive diffusion
37. Review of theoretical passive drug absorption models: Historical background, recent developments and limitations
38. Gastrointestinal absorption of drugs
39. The fluid mosaic model of the structure of cell membranes
40. Human jejunal effective permeability and its correlation with preclinical drug absorption models
41. Partition coefficients and their uses
42. Linear relationships between lipophilic character and biological activity of drugs
43. Lipophilic character and biological activity of drugs. II. Parabolic case
44. Computational approaches to lipophilicity: Methods and applications
45. A practitioner's perspective of the role of quantitative structure-activity analysis in medicinal chemistry
46. High lipophilicity decreases drug transport across intestinal epithelial cells
47. A novel method for measuring membrane-water partition coefficients of hydrophobic organic chemicals: Comparison with 1-octanol-water partitioning
48. Patterns of nonelectrolyte permeability
49. Molecular forces governing nonelectrolyte permeation through cell membranes
50. Effect of molecular charge on intestinal epithelial drug transport: pH-Dependent transport of cationic drugs
51. Caco-2 monolayers in experimental and theoretical predictions of drug transport
52. Applications of the Caco-2 model in the design and development of orally active drugs: Elucidation of biochemical and physical barriers posed by the intestinal epithelium
53. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells
54. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestine) absorption in man - Fact or myth
55. Link between drug absorption solubility and permeability measurements in Caco-2 cells
56. In vitro permeability through Caco-2 cells is not quantitatively predicitve of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system
57. Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds
58. MDCK (Madin-Darby Canine Kidney) cells: A tool for membrane permeability screening
59. Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats
60. Physicochemical high throughput screening: Parallel artificial membrane permeation assay in the description of passive absorption processes
61. The absolute oral bioavailability of selected drugs
62. The properties of known drugs. 1. Molecular frameworks
63. The human intestinal epithelial cell line Caco-2; pharmacological and pharmacokinetic applications
64. The influence of culture time and passage number on the morphological and physiological development of Caco-2 cells
65. Human intestinal epithelial cell monolayers as prescreens for oral drug delivery
66. Analysis of drug permeation across Caco-2 monolayer: Implication for predicting in vivo drug absorption
67. Intestinal absorption screening of mixtures from combinatorial libraries in the Caco-2 model
68. Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods: An analysis of ALOGP and CLOGP methods
69. Principal component analysis
70. Octanol-water partition: Searching for predictive models
71. Principal components and factor analysis: Part I - Principal components
72. Outlier detection in multivariate analytical chemical data
73. Carrier-mediated intestinal transport of drugs
74. Intestinal uptake of β-lactam antibiotics and its relationship to peptide transport
75. Intestinal transport of β-lactam antibiotics: Analysis of the affinity at the H+/ peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux
76. Transport mechanism of some naturally occurring tetracyclines across everted rat gut
77. Effect of amoxicillin, cephalexin, and tetracycline-hydrochloride on intestinal lleucine transport in the rat in vivo
78. Structure-activity relationship of carbacephalosporins and cephalosporins: Antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells
79. Transport and binding of methotrexate in vivo
80. Competitive inhibition between folic acid and methotrexate for transport carrier in the rat small intestine
81. Evidence of competitive inhibition of methotrexate absorption by leucovorin calcium in rat small intestine
82. Cloning and characterization of the hepatocellular methotrexate transport system
83. Studies on the metabolism of D- and L-isomers of 3,4-dihydroxyphenylalanine (DOPA) V. mechanism of intestinal absorption of D- and L-DOPA-14C in rats
84. Intestinal absorption of tritium-labeled-digitalis glycosides in experimental animals and man
85. Drug interactions in intestinal absorption of 3H-digitoxin in rats
86. Epithelial cells in culture as a model for the intestinal transport of antimicrobial agents
87. A general pattern for substrate recognition by P-glycoprotein
88. Correlation of drug absorption with molecular surface properties
89. The discovery-development interface has become the new interfacial phenomenon