Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response

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 no...

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Autores: Fonseca, Francina, Torre Fornell, Rafael de la, Díaz, Laura, Pastor, Antoni, Cuyàs, Elisabet, Pizarro Lozano, Nieves, Khymenets, Olha, Farré Albaladejo, Magí, Torrens, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/61823
Acceso en línea:https://hdl.handle.net/2445/61823
Access Level:acceso abierto
Palabra clave:Metadona
Farmacocinètica
Metabolisme dels medicaments
Citocrom P-450
Resistència als medicaments
Proteïnes de membrana
Polimorfisme genètic
Methadone hydrochloride
Pharmacokinetics
Drugs metabolism
Cytochrome P-450
Drug resistance
Membrane proteins
Genetic polymorphisms
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spelling Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and responseFonseca, FrancinaTorre Fornell, Rafael de laDíaz, LauraPastor, AntoniCuyàs, ElisabetPizarro Lozano, NievesKhymenets, OlhaFarré Albaladejo, MagíTorrens, MartaMetadonaFarmacocinèticaMetabolisme dels medicamentsCitocrom P-450Resistència als medicamentsProteïnes de membranaPolimorfisme genèticMethadone hydrochloridePharmacokineticsDrugs metabolismCytochrome P-450Drug resistanceMembrane proteinsGenetic polymorphismsAlthough 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.Public Library of Science (PLoS)2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/61823Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0019527PLoS One, 2011, vol. 6, num. 5, p. e19527http://dx.doi.org/10.1371/journal.pone.0019527cc-by (c) Fonseca, Francina et al., 2011http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/618232026-05-27T06:46:51Z
dc.title.none.fl_str_mv Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
title Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
spellingShingle Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
Fonseca, Francina
Metadona
Farmacocinètica
Metabolisme dels medicaments
Citocrom P-450
Resistència als medicaments
Proteïnes de membrana
Polimorfisme genètic
Methadone hydrochloride
Pharmacokinetics
Drugs metabolism
Cytochrome P-450
Drug resistance
Membrane proteins
Genetic polymorphisms
title_short Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
title_full Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
title_fullStr Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
title_full_unstemmed Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
title_sort Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
dc.creator.none.fl_str_mv Fonseca, Francina
Torre Fornell, Rafael de la
Díaz, Laura
Pastor, Antoni
Cuyàs, Elisabet
Pizarro Lozano, Nieves
Khymenets, Olha
Farré Albaladejo, Magí
Torrens, Marta
author Fonseca, Francina
author_facet Fonseca, Francina
Torre Fornell, Rafael de la
Díaz, Laura
Pastor, Antoni
Cuyàs, Elisabet
Pizarro Lozano, Nieves
Khymenets, Olha
Farré Albaladejo, Magí
Torrens, Marta
author_role author
author2 Torre Fornell, Rafael de la
Díaz, Laura
Pastor, Antoni
Cuyàs, Elisabet
Pizarro Lozano, Nieves
Khymenets, Olha
Farré Albaladejo, Magí
Torrens, Marta
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Metadona
Farmacocinètica
Metabolisme dels medicaments
Citocrom P-450
Resistència als medicaments
Proteïnes de membrana
Polimorfisme genètic
Methadone hydrochloride
Pharmacokinetics
Drugs metabolism
Cytochrome P-450
Drug resistance
Membrane proteins
Genetic polymorphisms
topic Metadona
Farmacocinètica
Metabolisme dels medicaments
Citocrom P-450
Resistència als medicaments
Proteïnes de membrana
Polimorfisme genètic
Methadone hydrochloride
Pharmacokinetics
Drugs metabolism
Cytochrome P-450
Drug resistance
Membrane proteins
Genetic polymorphisms
description 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.
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/61823
url https://hdl.handle.net/2445/61823
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0019527
PLoS One, 2011, vol. 6, num. 5, p. e19527
http://dx.doi.org/10.1371/journal.pone.0019527
dc.rights.none.fl_str_mv cc-by (c) Fonseca, Francina et al., 2011
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Fonseca, Francina et al., 2011
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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