ArticleBritish journal of clinical pharmacology2009
Contribution of the activities of CYP3A, CYP2D6, CYP1A2 and other potential covariates to the disposition of methadone in patients undergoing methadone maintenance treatment.
Article in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 58 citations in OpenAlex.
- Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.Anesthesiology · 2015Trial
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Pharmacogenetics of Opioid Use Disorder Treatment.CNS drugs · 2018Review
- Pharmacogenetics of Methadone Response.Molecular diagnosis & therapy · 2018Review
- Current Concepts in Methadone Metabolism and Transport.Clinical pharmacology in drug development · 2017Article
- Alternative Sampling Strategies for Cytochrome P450 Phenotyping.Clinical pharmacokinetics · 2016Review
- Genetic determinants of fetal opiate exposure and risk of neonatal abstinence syndrome: Knowledge deficits and prospects for future research.Clinical pharmacology and therapeutics · 2015Review
- Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy.Frontiers in pharmacology · 2015Review
- Cytochrome P4503A does not mediate the interaction between methadone and ritonavir-lopinavir.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.Addiction biology · 2013Article
- A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice.Expert review of clinical pharmacology · 2013Review
- Role of cytochrome P4502B6 in methadone metabolism and clearance.Journal of clinical pharmacology · 2013Article
- Methadone and metabolites in hair of methadone-assisted pregnant women and their infants.Therapeutic drug monitoring · 2012Article
- Lack of indinavir effects on methadone disposition despite inhibition of hepatic and intestinal cytochrome P4503A (CYP3A).Anesthesiology · 2012Article
- Pharmacogenomic considerations in opioid analgesia.Pharmacogenomics and personalized medicine · 2012Article
- Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response.PloS one · 2011Article
- Stereo-selective metabolism of methadone by human liver microsomes and cDNA-expressed cytochrome P450s: a reconciliation.Basic & clinical pharmacology & toxicology · 2011Article
- Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of methadone in a sample of Iranian (mazandarani) opiate users undergoing methadone maintenance treatment.Iranian journal of psychiatry and behavioral sciences · 2011Article
- Biological pathways and genetic variables involved in pain.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2010Review
- Methadone: a substrate and mechanism-based inhibitor of CYP19 (aromatase).Drug metabolism and disposition: the biological fate of chemicals · 2010Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the influence of different cytochrome P450 (CYP) activities and other potential covariates on the disposition of methadone in patients on methadone maintenance therapy (MMT).
methodsEighty-eight patients (58 male; 21-55 years; 84 White) on MMT were studied. CYP2D6 activity [3 h plasma metabolic ratio of dextromethorphan (DEX) to dextrorphan (DOR)] was determined in 44 patients (29 male; 24-55 years), CYP1A2 activity (salivary caffeine elimination half-life) in 44 patients (21 male; 24-55 years) and CYP3A activity (oral clearance of midazolam) in 49 patients (33 male; 23-55 years). Data on all three CYPs were obtained from 32 subjects. Total plasma concentrations of (RS)-methadone and total and unbound plasma concentrations of both enantiomers were measured by LC/MS. Population pharmacokinetics and subsequent multiple regression analysis were used to calculate methadone oral clearance and to identify its covariates.
resultsBetween 61 and 68% of the overall variation in total plasma trough concentrations of (RS)-, (R)- and (S)-methadone was explained by methadone dose, duration of addiction before starting MMT, CYP3A activity and illicit morphine use. CYP3A activity explained 22, 16, 15 and 23% of the variation in unbound (R)-, unbound (S)-, total (RS)- and total (S)-methadone clearances, respectively. Neither CYP2D6 nor CYP1A2 activity was related to methadone disposition.
conclusionsCYP3A activity has a modest influence on methadone disposition. Inhibitors and inducers of this enzyme should be monitored in patients taking methadone.
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