Comparative QSAR studies on PAMPA/modified PAMPA for high throughput profiling of drug absorption potential with respect to Caco-2 cells and human intestinal absorption

Despite the dramatic increase in speed of synthesis and biological evaluation of new chemical entities, the number of compounds that survive the rigorous processes associated with drug development is low. Thus, an increased emphasis on thorough ADMET (absorption, distribution, metabolism, excretion and toxicity) studies based on in vitro and in silico approaches allows for early evaluation of new drugs in the development phase. Artificial membrane permeability measurements afford a high throughput, relatively low cost but labor intensive alternative for in vitro determination of drug absorption potential; parallel artificial membrane permeability assays have been extensively utilized to determine drug absorption potentials. The present study provides comparative QSAR analysis on PAMPA/modified PAMPA for high throughput profiling of drugs with respect to Caco-2 cells and human intestinal absorption.

[1]  S. Ekins,et al.  Progress in predicting human ADME parameters in silico. , 2000, Journal of pharmacological and toxicological methods.

[2]  Kiyohiko Sugano,et al.  Prediction of human intestinal permeability using artificial membrane permeability. , 2003, International journal of pharmaceutics.

[3]  I. Hidalgo,et al.  Assessing the absorption of new pharmaceuticals. , 2001, Current topics in medicinal chemistry.

[4]  E. Kerns,et al.  High throughput physicochemical profiling for drug discovery. , 2001, Journal of pharmaceutical sciences.

[5]  R. M. Muir,et al.  Correlation of Biological Activity of Phenoxyacetic Acids with Hammett Substituent Constants and Partition Coefficients , 1962, Nature.

[6]  Kazuya Nakao,et al.  Relationships between structure and high-throughput screening permeability of diverse drugs with artificial membranes: application to prediction of Caco-2 cell permeability. , 2005, Bioorganic & medicinal chemistry.

[7]  M. Machida,et al.  High Throughput Prediction of Oral Absorption: Improvement of the Composition of the Lipid Solution Used in Parallel Artificial Membrane Permeation Assay , 2001, Journal of biomolecular screening.

[8]  Kin-Kai Hwang,et al.  A comparative study of artificial membrane permeability assay for high throughput profiling of drug absorption potential. , 2002, European journal of medicinal chemistry.

[9]  Kiyohiko Sugano,et al.  Prediction of passive intestinal absorption using bio-mimetic artificial membrane permeation assay and the paracellular pathway model. , 2002, International journal of pharmaceutics.

[10]  K Gubernator,et al.  Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes. , 1998, Journal of medicinal chemistry.

[11]  Stephen R. Johnson,et al.  Molecular properties that influence the oral bioavailability of drug candidates. , 2002, Journal of medicinal chemistry.

[12]  E. Lien,et al.  QSAR analysis of membrane permeability to organic compounds. , 1996, Journal of drug targeting.

[13]  Li Di,et al.  Combined application of parallel artificial membrane permeability assay and Caco-2 permeability assays in drug discovery. , 2004, Journal of pharmaceutical sciences.

[14]  Tudor I. Oprea,et al.  Property distribution of drug-related chemical databases* , 2000, J. Comput. Aided Mol. Des..

[15]  K. Luthman,et al.  Correlation of drug absorption with molecular surface properties. , 1996, Journal of pharmaceutical sciences.

[16]  C. Selassie,et al.  QSAR: then and now. , 2002, Current topics in medicinal chemistry.

[17]  D. E. Clark,et al.  Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration. , 1999, Journal of pharmaceutical sciences.

[18]  Ulrich J. Krull,et al.  The structure and electrochemical properties of a polymer-supported lipid biosensor , 1980 .

[19]  D. E. Patterson,et al.  Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR Studies , 1988 .

[20]  U Norinder,et al.  Theoretical calculation and prediction of drug transport processes using simple parameters and partial least squares projections to latent structures (PLS) statistics. The use of electrotopological state indices. , 2001, Journal of pharmaceutical sciences.

[21]  J. Goodwin,et al.  Physicochemical determinants of passive membrane permeability: role of solute hydrogen-bonding potential and volume. , 2001, Journal of medicinal chemistry.

[22]  D. E. Clark,et al.  Prediction of intestinal absorption and blood-brain barrier penetration by computational methods. , 2001, Combinatorial chemistry & high throughput screening.

[23]  P J Sinko,et al.  Development of predictive pharmacokinetic simulation models for drug discovery. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[24]  A. Leo,et al.  Chem-bioinformatics: comparative QSAR at the interface between chemistry and biology. , 2002, Chemical reviews.

[25]  P. Proulx Structure-function relationships in intestinal brush border membranes. , 1991, Biochimica et biophysica acta.

[26]  C. Hansch,et al.  Comparative QSAR and the radical toxicity of various functional groups. , 2002, Chemical reviews.

[27]  Thomas J. Vidmar,et al.  A non-aqueous partitioning system for predicting the oral absorption potential of peptides , 1994 .

[28]  T I Oprea,et al.  Toward minimalistic modeling of oral drug absorption. , 1999, Journal of molecular graphics & modelling.

[29]  P. Mura,et al.  Development and evaluation of an in vitro method for prediction of human drug absorption II. Demonstration of the method suitability. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[30]  B. Testa,et al.  Physicochemical profiling in drug research: a brief survey of the state-of-the-art of experimental techniques , 2002, Cellular and Molecular Life Sciences CMLS.

[31]  Li Di,et al.  High throughput artificial membrane permeability assay for blood-brain barrier. , 2003, European journal of medicinal chemistry.

[32]  K. Terada,et al.  Optimized conditions of bio-mimetic artificial membrane permeation assay. , 2001, International journal of pharmaceutics.

[33]  B. Faller,et al.  High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes. , 2001, Journal of medicinal chemistry.