Observational studyBritish journal of clinical pharmacology2015
Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity.
Observational study in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00894452 (Factors Associated With the Variance of Oral Methadone Dosage at Steady State of Maintenance Treatment), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Factors Associated With the Variance of Oral Methadone Dosage at Steady State of Maintenance Treatment: Description of Bio-markers of Phenotype and Genotype.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.Journal of clinical laboratory analysis · 2022Pooled it
- Investigating Changes in Liver Enzyme Levels in Patients With Acute Methadone Poisoning.Journal of toxicology · 2026Article
- ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of their influence on plasma methadone levels and clinical response to methadone maintenance treatment in opioid use disorder.Fundamental & clinical pharmacology · 2025Article
- The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- An epigenetic candidate-gene association study of parental styles in suicide attempters with substance use disorders.Addiction biology · 2024Article
- Developmental outcomes with perinatal exposure (DOPE) to prescription opioids.NeuroImmune pharmacology and therapeutics · 2023Review
- The Role of Pharmacogenomics in Opioid Prescribing.Current treatment options in oncology · 2022Review
- Frontal Lobe Functions, Demoralization, Depression and Craving as Prognostic Factors and Positive Outcomes of Patients with Heroin Use Disorder Receiving 6 Months of Methadone Maintenance Treatment.International journal of environmental research and public health · 2022Article
- Methylation quantitative trait locus rs5326 is associated with susceptibility and effective dosage of methadone maintenance treatment for heroin use disorder.Psychopharmacology · 2021Article
- Novel associations betweenPharmacogenomics · 2021Observational
- Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway.Substance abuse treatment, prevention, and policy · 2021Article
- Risk Assessment for Heroin Use and Craving Score Using Polygenic Risk Score.Journal of personalized medicine · 2021Article
- Scotland's 2009-2015 methadone-prescription cohort: Quintiles for daily dose of prescribed methadone and risk of methadone-specific death.British journal of clinical pharmacology · 2021Article
- Clustering suicidal phenotypes and genetic associations with brain-derived neurotrophic factor in patients with substance use disorders.Translational psychiatry · 2021Article
- Translational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances.Translational psychiatry · 2020Article
- Review
- Article
- Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study.British journal of clinical pharmacology · 2019Observational
- Review
- Liver damage indices as a tool for modifying methadone maintenance treatment: a cross-sectional study.Croatian medical journal · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsMethadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients.
methodsEighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day(-1) methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes.
resultsMethadone maintenance dose was correlated to the highest dose ever used (r(2) = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27-18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01-2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day(-1) in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs ] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = -0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose.
conclusionsMethadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP3A4 activity in stable patients.
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Registered trials
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