Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
7254748
Reference Type
Journal Article
Title
Structure-based prediction of human intestinal membrane permeability for rapid in silico BCS classification
Author(s)
Sun, L; Liu, X; Xiang, R; Wu, C; Wang, Y; Sun, Y; Sun, J; He, Z; ,
Year
2013
Is Peer Reviewed?
Yes
Journal
Biopharmaceutics and Drug Disposition
ISSN:
0142-2782
EISSN:
1099-081X
Language
English
PMID
23716273
DOI
10.1002/bdd.1848
Abstract
Human effective intestinal membrane permeability (Peff) is one of the two important indicators for drug classification according to the Biopharmaceutical Classification System (BCS), and contributes greatly to the performance of oral drug absorption. Here, a structure-based in silico predictive model of Peff was developed successfully to facilitate in silico BCS classification in the early stage of drug discovery, even before the compound was synthesized. The quantitative structure-Peff relationship for 30 drugs was constructed based on seven structural parameters. Then the model was built by the multiple linear regression method and internally validated by the residual analysis, the normal probability-probability plot and the Williams plot. For the entire data set, the R² and adjusted R² values were 0.782 and 0.712, respectively. The results indicated that the fitted model was robust, stable and satisfied all the prerequisites of the regression models. As for the 102 tested drugs, the predicted Peff values had a good correlation with the experimental human absorbed fraction (Fa). This model was also used to perform high/low Peff classification for 57 drugs that have been classified according to the BCS, and 72% of drugs could be classified correctly, indicating that the developed model can be used for rapid BCS classification in the early stages of drug discovery.
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity