In:
Pharmacology, S. Karger AG, Vol. 80, No. 4 ( 2007), p. 304-311
Abstract:
Methadone and 〈 i 〉 L 〈 /i 〉 -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 〈 i 〉 ABCB1 〈 /i 〉 gene, and whether methadone transport exhibits stereoselectivity. Pig kidney epithelial cells (control) and human 〈 i 〉 ABCB1 〈 /i 〉 -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 〈 i 〉 ABCB1 〈 /i 〉 -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.
Type of Medium:
Online Resource
ISSN:
0031-7012
,
1423-0313
Language:
English
Publisher:
S. Karger AG
Publication Date:
2007
detail.hit.zdb_id:
1483550-2
SSG:
15,3
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