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Original Paper

In vitro P-Glycoprotein-Mediated Transport of (R)-, (S)-, (R,S)-Methadone, LAAM and Their Main Metabolites

Crettol S. · Digon P. · Powell Golay K. · Brawand M. · Eap C.B.

Author affiliations

Unité de Biochimie et Psychopharmacologie Clinique, Centre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Hôpital de Cery, Prilly-Lausanne, Suisse

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Pharmacology 2007;80:304–311

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: May 29, 2007
Accepted: June 01, 2007
Published online: August 09, 2007
Issue release date: October 2007

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 2

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

Methadone and L-α-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.

© 2007 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: May 29, 2007
Accepted: June 01, 2007
Published online: August 09, 2007
Issue release date: October 2007

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 2

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA


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