Skip Navigation


ToxSci Advance Access originally published online on September 14, 2005
Toxicological Sciences 2005 88(2):434-446; doi:10.1093/toxsci/kfi319
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
88/2/434    most recent
kfi319v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Li, Y.
Right arrow Articles by Hopfinger, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, Y.
Right arrow Articles by Hopfinger, A. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A Study of the Relationship between Cornea Permeability and Eye Irritation Using Membrane-Interaction QSAR Analysis

Yi Li, Jianzhong Liu, Dahua Pan and A. J. Hopfinger1

Laboratory of Molecular Modeling and Design (MC 781), College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612-7231

Received July 7, 2005; accepted September 6, 2005

A methodology termed membrane-interaction QSAR (MI-QSAR) analysis has been used to develop QSAR models to predict drug permeability coefficients across cornea and its component layers (epithelium, stroma, and endothelium). From a training set of 25 structurally diverse drugs, significant QSAR models are constructed and compared for the permeability of the cornea, epithelium, and stroma plus endothelium. Cornea permeability is found to depend on the measured distribution coefficient of the drug, the cohesive energy of the drug, the total potential energy of the drug-membrane "complex," and three other energy refinement descriptor terms. The endothelium may be a more important barrier in cornea permeation than the stroma. Moreover, an investigation of the correlation between cornea permeation and eye irritation is presented as an example of a cross study on different ADMET properties using MI-QSAR analysis. Thirteen structurally diverse drugs, whose molar-adjusted eye irritation scores (MES) have been measured using the Draize rabbit-eye test, were chosen as an eye irritation comparison set. A poor correlation (R2 = 0.0232) between the MES measures and the predicted cornea permeability coefficients for the drugs in the eye irritation set suggests there is no significant relationship between eye irritation potency and the cornea permeability.

Key Words: cornea permeability; eye irritation; membrane-interaction quantitative structure-activity relationships (MI-QSAR).


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.