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

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. Copyright (c) 2007 S. Karger AG, Basel.