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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 principales: Fonseca, Francina, de la Torre, Rafael, Díaz, Laura, Pastor, Antonio, Cuyàs, Elisabet, Pizarro, Nieves, Khymenets, Olha, Farré, Magí, Torrens, Marta
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093392/
https://www.ncbi.nlm.nih.gov/pubmed/21589866
http://dx.doi.org/10.1371/journal.pone.0019527
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author Fonseca, Francina
de la Torre, Rafael
Díaz, Laura
Pastor, Antonio
Cuyàs, Elisabet
Pizarro, Nieves
Khymenets, Olha
Farré, Magí
Torrens, Marta
author_facet Fonseca, Francina
de la Torre, Rafael
Díaz, Laura
Pastor, Antonio
Cuyàs, Elisabet
Pizarro, Nieves
Khymenets, Olha
Farré, Magí
Torrens, Marta
author_sort Fonseca, Francina
collection PubMed
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, [4(th) 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.
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spelling pubmed-30933922011-05-17 Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response Fonseca, Francina de la Torre, Rafael Díaz, Laura Pastor, Antonio Cuyàs, Elisabet Pizarro, Nieves Khymenets, Olha Farré, Magí Torrens, Marta PLoS One Research Article 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, [4(th) 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 2011-05-12 /pmc/articles/PMC3093392/ /pubmed/21589866 http://dx.doi.org/10.1371/journal.pone.0019527 Text en Fonseca et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Fonseca, Francina
de la Torre, Rafael
Díaz, Laura
Pastor, Antonio
Cuyàs, Elisabet
Pizarro, Nieves
Khymenets, Olha
Farré, Magí
Torrens, Marta
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
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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093392/
https://www.ncbi.nlm.nih.gov/pubmed/21589866
http://dx.doi.org/10.1371/journal.pone.0019527
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