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Title: Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
Author: Fonseca, Francina
Torre Fornell, Rafael de la
Díaz, Laura
Pastor Bosch, Antonio
Cuyàs, Elisabet
Pizarro Lozano, Nieves
Khymenets, Olha
Farré Albaladejo, Magí
Torrens, Marta
Keywords: Metadona
Metabolisme dels medicaments
Citocrom P-450
Resistència als medicaments
Proteïnes de membrana
Polimorfisme genètic
Methadone hydrochloride
Drugs metabolism
Cytochrome P-450
Drug resistance
Membrane proteins
Genetic polymorphisms
Issue Date: 12-May-2011
Publisher: Public Library of Science (PLoS)
Abstract: Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2011, vol. 6, num. 5, p. e19527
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

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