The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution.

Details

Serval ID
serval:BIB_B9CC1CA46639
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution.
Journal
Expert Opinion On Drug Metabolism and Toxicology
Author(s)
Choong E., Dobrinas M., Carrupt P.A., Eap C.B.
ISSN
1744-7607[electronic], 1742-5255[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
6
Number
8
Pages
953-965
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
IMPORTANCE OF THE FIELD: The permeability glycoprotein (P-gp) is an important protein transporter involved in the disposition of many drugs with different chemical structures, but few studies have examined a possible stereoselectivity in its activity. P-gp can have a major impact on the distribution of drugs in selected organs, including the brain. Polymorphisms of the ABCB1 gene, which encodes for P-gp, can influence the kinetics of several drugs. AREAS COVERED IN THIS REVIEW: A search including publications from 1990 up to 2009 was performed on P-gp stereoselectivity and on the impact of ABCB1 polymorphisms on enantiomer brain distribution. WHAT THE READER WILL GAIN: Despite stereoselectivity not being expected because of the large variability of chemical structures of P-gp substrates, structure-activity relationships suggest different P-gp-binding sites for enantiomers. Enantioselectivity in the activity of P-gp has been demonstrated by in vitro studies and in animal models (preferential transport of one enantiomer or different inhibitory potencies towards P-gp activity between enantiomers). There is also in vivo evidence of an enantioselective drug transport at the human blood-brain barrier. TAKE HOME MESSAGE: The significant enantioselective activity of P-gp might be clinically relevant and must be taken into account in future studies.
Pubmed
Web of science
Create date
23/08/2010 13:18
Last modification date
20/08/2019 15:27
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