Document Detail

Drug discovery and regulatory considerations for improving in silico and in vitro predictions that use Caco-2 as a surrogate for human intestinal permeability measurements.
MedLine Citation:
PMID:  23344793     Owner:  NLM     Status:  MEDLINE    
There is a growing need for highly accurate in silico and in vitro predictive models to facilitate drug discovery and development. Results from in vitro permeation studies across the Caco-2 cell monolayer are commonly used for drug permeability screening in industry and are also accepted as a surrogate for human intestinal permeability measurements by the US FDA to support new drug applications. Countless studies carried out in this cell line with published permeability measurements have enabled the development of many in silico prediction models. We identify several common cases that illustrate how using Caco-2 permeability measurements in these in silico and in vitro predictive models will not correlate with human intestinal permeability and will further lead to inaccuracies in these models. We provide guidelines and recommendations for improving these models to more accurately predict clinically relevant information, thereby enhancing the drug discovery, development, and regulatory approval processes.
Caroline A Larregieu; Leslie Z Benet
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  The AAPS journal     Volume:  15     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-10-22     Revised Date:  2014-04-29    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  483-97     Citation Subset:  IM    
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MeSH Terms
Caco-2 Cells
Computer Simulation*
Drug Approval / methods*
Drug Discovery / methods*,  standards
Guidelines as Topic
Intestinal Absorption*
Intestines / metabolism*
Models, Biological*
Pharmaceutical Preparations / chemistry,  metabolism*
Quality Control
Reproducibility of Results
Grant Support
Reg. No./Substance:
0/Pharmaceutical Preparations

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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