In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites

Details

Serval ID
serval:BIB_7DD3F39D7F18
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites
Journal
Pharmacology
Author(s)
Crettol Séverine, Digon Patricia, Powell Golay Kerry, Brawand Marlyse, Eap Chin-Bin
ISSN
0031-7012
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
80
Number
4
Pages
304-311
Language
english
Notes
SAPHIRID:64698
Abstract
Methadone and L-alpha-acetylmethadol (LAAM) are used as treatment for opiate addiction. Using a cellular model, we aimed to determine if methadone, LAAM and their main metabolites are substrates of the human P-glycoprotein transporter (P-gp), which is encoded by the ABCB1 gene, and whether methadone transport exhibits stereoselectivity. Pig kidney epithelial cells (control) and human ABCB1-transfected cells were incubated with methadone, LAAM and their metabolites, and their intra- and extracellular concentrations were measured. The intra- to extracellular ratios of methadone, LAAM and their metabolites were all decreased in ABCB1-transfected cells compared to controls (p < 0.05), thus indicating that they are substrates of P-gp. A weak stereoselectivity in methadone transport was observed towards the (S)-enantiomer. P-gp may therefore affect the pharmacokinetics and pharmacodynamics of methadone and LAAM. (c) 2007 S. Karger AG, Basel.
Pubmed
Web of science
Create date
10/03/2008 10:53
Last modification date
20/08/2019 14:39
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