ArticleJournal of clinical pharmacology2013
Role of cytochrome P4502B6 in methadone metabolism and clearance.
Article in Journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review.Drug design, development and therapy · 2015Pooled it
- Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease.Pediatric blood & cancer · 2016Trial
- Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.Anesthesiology · 2015Trial
- The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Methadone and Buprenorphine in the Perioperative Setting: A Review of the Literature.Current pain and headache reports · 2024Review
- Drug-Drug Interaction Studies of Esmethadone (REL-1017) Involving CYP3A4- and CYP2D6-Mediated Metabolism.Drugs in R&D · 2024Article
- Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Influence ofLife (Basel, Switzerland) · 2023Article
- Quantitative Prediction of Drug Interactions Caused by Cytochrome P450 2B6 Inhibition or Induction.Clinical pharmacokinetics · 2022Article
- Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis.Electrophoresis · 2021Article
- The phenomics and genetics of addictive and affective comorbidity in opioid use disorder.Drug and alcohol dependence · 2021Review
- Pharmacogenomics biomarkers for personalized methadone maintenance treatment: The mechanism and its potential use.Bosnian journal of basic medical sciences · 2021Review
- Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences.PloS one · 2021Article
- Methadone for Pain Management: A Pharmacotherapeutic Review.CNS drugs · 2020Review
- Article
- Methadone Disposition: Implementing Lessons Learned.Journal of clinical pharmacology · 2019Article
- Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study.British journal of clinical pharmacology · 2019Observational
- Methadone dosing strategies in preterm neonates can be simplified.British journal of clinical pharmacology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Methadone N-demethylation in vitro is catalyzed by hepatic cytochrome P4502B6 (CYP2B6) and CYP3A4, but clinical disposition is often attributed to CYP3A4. This investigation tested the hypothesis that CYP2B6 is a prominent CYP isoform responsible for clinical methadone N-demethylation and clearance, using the in vivo mechanism-based CYP2B6 inhibitor ticlopidine, given orally for 4 days. A preliminary clinical investigation with the CYP3A4/5 substrate probe alfentanil established that ticlopidine did not inhibit intestinal or hepatic CYP3A4/5. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone before and after ticlopidine. Ticlopidine significantly and stereoselectively (S > R) inhibited methadone N-demethylation, decreasing plasma metabolite/methadone area under the curve ratios and metabolite formation clearances. Ticlopidine also significantly increased the dose-adjusted plasma area under the curve for R- and S-methadone by 20% and 60%, respectively, after both intravenous and oral dosing. CYP2B6 inhibition reduces methadone N-demethylation and clearance, and alters methadone concentrations, demonstrating an important role for CYP2B6 in clinical methadone disposition.
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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.