ArticleDrug and alcohol dependence2014
Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study.
Article in Drug and alcohol dependence, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses 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.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.Journal of clinical laboratory analysis · 2022Pooled it
- Effects of CYP2B6 polymorphisms on plasma nevirapine concentrations: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients.Expert review of clinical pharmacology · 2019Trial
- Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients.Clinical pharmacokinetics · 2016Trial
- Article
- The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Biomarker-Driven Pharmacokinetics and Efficacy of Polymyxin B in Critically Ill Patients with XDR-GN Pneumonia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- A Systematic Review on Antimicrobial Pharmacokinetic Differences between Asian and Non-Asian Adult Populations.Antibiotics (Basel, Switzerland) · 2023Review
- Findings from a pilot study of buprenorphine population pharmacokinetics: A potential effect of HIV on buprenorphine bioavailability.Drug and alcohol dependence · 2022Article
- The Role of Pharmacogenomics in Opioid Prescribing.Current treatment options in oncology · 2022Review
- Prevalence of Domestic Violence Against Women Undergoing Methadone Maintenance Therapy Programs and its Related Risk Factors.Addiction & health · 2022Article
- Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity.CPT: pharmacometrics & systems pharmacology · 2022Article
- A genetic-based population PK/PD modeling of methadone in Chinese opiate dependence patients.European journal of clinical pharmacology · 2022Article
- Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children.CPT: pharmacometrics & systems pharmacology · 2021Article
- Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study.Drug and alcohol dependence · 2021Article
- CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations-Implication for Drug Safety, Dosing, and Individualized Therapy.Frontiers in genetics · 2021Review
- Pharmacogenomics of methadone: a narrative review of the literature.Pharmacogenomics · 2020Review
- Pharmacological Prevention of Neonatal Opioid Withdrawal in a Pregnant Guinea Pig Model.Frontiers in pharmacology · 2020Article
- Development and Psychometric Assessment of the Methadone Therapy Experiences Questionnaire among Patients under Treatment.Addiction & health · 2019Article
- Pharmacogenetics of Opioid Use Disorder Treatment.CNS drugs · 2018Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTreatment of opiate use disorders with methadone is complicated by wide interindividual variability in pharmacokinetics. To identify potentially contributing covariates in methadone pharmacokinetics, we used population pharmacokinetic modeling to estimate clearance (CL/F) and volume of distribution (V/F) for each methadone enantiomer in an ethnically diverse methadone maintained population.
methodsPlasma levels of the opiate-active R-methadone and opiate-inactive S-methadone were measured in 206 methadone maintained subjects approximately two and twenty-three hours after a daily oral dose of rac-methadone. A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction (FOCE-I) was used to evaluate methadone CL/F and V/F. The influence of covariates on parameter estimates was evaluated using stepwise covariate modeling. Covariates included ethnicity, gender, weight, BMI, age, methadone dose, and 21 single nucleotide polymorphisms in genes implicated in methadone pharmacokinetics.
resultsIn the final model, for each enantiomer, Hmong ethnicity reduced CL/F by approximately 30% and the rs2032582 (ABCB1 2677G>T/A) GG genotype was associated with a 20% reduction in CL/F. The presence of the rs3745274 minor allele (CYP2B6 515G>T) reduced CL/F by up to 20% for S-methadone only. A smaller effect of age was noted on CL/F for R-methadone.
conclusionThis is the first report showing the influence of the rs2032582 and rs3745274 variants on methadone pharmacokinetics rather than simply dose requirements or plasma levels. Population pharmacokinetics is a valuable method for identifying the influences on methadone pharmacokinetic variability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.