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    
Abstract/OtherAbstract:
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.
Authors:
Caroline A Larregieu; Leslie Z Benet
Related Documents :
23480483 - Intestinal bile secretion promotes drug absorption from lipid colloidal phases via indu...
21612153 - Stavudine entrapped lipid nanoparticles for targeting lymphatic hiv reservoirs.
23898223 - Organelle targeting: third level of drug targeting.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Caco-2 Cells
Computer Simulation*
Drug Approval / methods*
Drug Discovery / methods*,  standards
Guidelines as Topic
Humans
Intestinal Absorption*
Intestines / metabolism*
Models, Biological*
Permeability
Pharmaceutical Preparations / chemistry,  metabolism*
Quality Control
Reproducibility of Results
Grant Support
ID/Acronym/Agency:
GM-61390/GM/NIGMS NIH HHS; P30 DK026743/DK/NIDDK NIH HHS; T32-GM007175/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations
Comments/Corrections

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


Previous Document:  The interaction of fatty acid amide hydrolase (FAAH) inhibitors with an anandamide carrier protein u...
Next Document:  Educational Differences in Completed Fertility: A Behavioral Genetic Study of Finnish Male and Femal...