Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
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- dc.contributor.author Fonseca Casals, Francina, 1972-ca
- dc.contributor.author Torre Fornell, Rafael de laca
- dc.contributor.author Díaz, Lauraca
- dc.contributor.author Pastor, Antonioca
- dc.contributor.author Cuyàs, Elisabetca
- dc.contributor.author Pizarro Lozano, Mª Nievesca
- dc.contributor.author Khymenets, Olha, 1974-ca
- dc.contributor.author Farré Albaladejo, Magíca
- dc.contributor.author Torrens, Martaca
- dc.date.accessioned 2015-04-30T07:11:28Z
- dc.date.available 2015-04-30T07:11:28Z
- dc.date.issued 2011ca
- dc.description.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.en
- dc.description.sponsorship Financial support was received from the TV3 Marató (01/810), Fondo de Investigaciones Sanitarias de la Seguridad Social, FIS (PI040632, PI040619), and the Instituto Carlos III (RTA 06/0001/1009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
- dc.format.mimetype application/pdfca
- dc.identifier.citation Fonseca F, de la Torre R, Diaz L, Pastor A, Cuyas E, Pizarro N et al. Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. PLoS ONE. 2011;6(5):e19527. DOI: 10.1371/journal.pone.0019527ca
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0019527
- dc.identifier.issn 1932-6203ca
- dc.identifier.uri http://hdl.handle.net/10230/23501
- dc.language.iso engca
- dc.publisher Public Library of Science (PLoS)ca
- dc.relation.ispartof PLoS ONE. 2011;6(5):e19527
- dc.rights © 2011 Fonseca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Drogoaddiccióca
- dc.subject.other Metadona -- Ús terapèuticca
- dc.title Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and responseen
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca