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Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response
- Source :
- Recercat. Dipósit de la Recerca de Catalunya, instname, PLoS ONE, Dipòsit Digital de la UB, Universidad de Barcelona, PLoS ONE, Vol 6, Iss 5, p e19527 (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. 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 manuscript
- Subjects :
- Male
Pharmacology
Biochemistry
Drug Metabolism
Cytochrome P-450 Enzyme System
Metadona -- Ús terapèutic
Cytochrome P-450
Membrane proteins
Psychology
Drug Dependence
Psychiatry
Multidisciplinary
medicine.diagnostic_test
Substance Abuse
Proteïnes de membrana
Drugs metabolism
Middle Aged
Mental Health
Behavioral Pharmacology
Blood Chemistry
Medicine
Metabolisme dels medicaments
Female
medicine.drug
Research Article
Adult
CYP2D6
medicine.medical_specialty
Methadone maintenance
Drugs and Devices
ATP Binding Cassette Transporter, Subfamily B
Urinalysis
Science
CYP2C19
Genetic polymorphisms
Methadone hydrochloride
Pharmacokinetics
Internal medicine
Metadona
medicine
Drogoaddicció
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
Biology
Alleles
Resistència als medicaments
Behavior
Dose-Response Relationship, Drug
Farmacocinètica
business.industry
Polimorfisme genètic
Opioid-Related Disorders
Citocrom P-450
Metabolism
Opioid
Pharmacogenetics
Drug resistance
business
Methadone
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Recercat. Dipósit de la Recerca de Catalunya, instname, PLoS ONE, Dipòsit Digital de la UB, Universidad de Barcelona, PLoS ONE, Vol 6, Iss 5, p e19527 (2011)
- Accession number :
- edsair.doi.dedup.....bf78df98e919c3b8d29738d64e7cc435