ArticleJournal of analytical toxicology2014
Fatal methadone toxicity: potential role of CYP3A4 genetic polymorphism.
Article in Journal of analytical toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Pharmacogenetic Evidence in Opioid-Related Toxicity and Death with an Appraisal of Emerging Multi-Omics Studies: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Comparison of Molecular Techniques for Improving the Methodology in the Laboratory of Pharmacogenetics.International journal of molecular sciences · 2024Article
- Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study.Journal of personalized medicine · 2023Article
- 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
- ABCB1, CYP2B6, and CYP3A4 genetic polymorphisms do not affect methadone maintenance treatment in HCV-positive patients.Arhiv za higijenu rada i toksikologiju · 2020Article
- Pharmacogenomics of methadone: a narrative review of the literature.Pharmacogenomics · 2020Review
- Characterizing Fentanyl Variability Using Population Pharmacokinetics in Pediatric Burn Patients.Journal of burn care & research : official publication of the American Burn Association · 2020Observational
- Effects of cytochrome P450 single nucleotide polymorphisms on methadone metabolism and pharmacodynamics.Biochemical pharmacology · 2018Review
- Pharmacogenetics of Opioid Use Disorder Treatment.CNS drugs · 2018Review
- Pharmacogenetics of Methadone Response.Molecular diagnosis & therapy · 2018Review
- The Promise of Molecular Autopsy in Forensic Pathology Practice.Academic forensic pathology · 2017Article
- Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities.Journal of analytical toxicology · 2017Article
- Article
- Clinical Presentation and the Outcome of Therapy in a Cohort of Patients with Methadone Toxicity in Iran.Materia socio-medica · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype.
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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.