Document Detail

Utility of 96 well Caco-2 cell system for increased throughput of P-gp screening in drug discovery.
MedLine Citation:
PMID:  15207543     Owner:  NLM     Status:  MEDLINE    
The use of Caco-2 cells for screening of discovery compounds for their permeability characteristics and P-glycoprotein interactions is well established and used routinely in pharmaceutical industries world-wide. The screening model involves growing cells on 12 or 24 well transwell format. In this manuscript, we report the use of Caco-2 cells grown on 96 well transwell plates for screening compounds for their potential to interact with P-gp. Bi-directionality studies were performed with known P-gp substrates such as saquinavir, indinavir, vinblastine, vincristine, verapamil, digoxin and taxol. P-gp inhibition studies were also conducted using radiolabeled digoxin as the probe. The results demonstrated that P-gp substrates had efflux ratios (Pc (B to A)/Pc (A to B)) in the 96 well format that were comparable to the ratios seen in 12 and 24 well format. Inhibition of digoxin efflux transport in presence of the test compounds (P-gp substrates) demonstrated that 96 well cells express adequate amounts of efflux transporters and perform as well as the 12 and 24 well Caco-2 cells. Thus, the 96 well Caco-2 cell set-up presents a higher throughput permeability model capable of identifying compounds that interact with P-gp and has the potential to significantly increase the efficiency of P-gp screening in early drug discovery.
Praveen V Balimane; Karishma Patel; Anthony Marino; Saeho Chong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V     Volume:  58     ISSN:  0939-6411     ISO Abbreviation:  Eur J Pharm Biopharm     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-21     Completed Date:  2005-01-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9109778     Medline TA:  Eur J Pharm Biopharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  99-105     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Elsevier B.V.
Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, NJ, USA.
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MeSH Terms
Caco-2 Cells
Cell Membrane Permeability
Drug Design*
Drug Evaluation, Preclinical / instrumentation*,  methods*
P-Glycoprotein / metabolism*
Pharmaceutical Preparations / metabolism*
Reg. No./Substance:
0/P-Glycoprotein; 0/Pharmaceutical Preparations

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