ArticleBritish journal of clinical pharmacology2012
Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects.
Article in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 32 citations in OpenAlex.
- Coordinated P450-UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa.PLoS biology · 2026Article
- Roles of Uridine Diphosphoglucuronosyltransferase 2B Enzymes in Cancer Susceptibility and Treatment: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Combined in vivo metabolic effects of quetiapine and methadone in brain and blood of rats.Archives of toxicology · 2024Article
- Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions.The Journal of pharmacology and experimental therapeutics · 2023Review
- Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths.International journal of legal medicine · 2021Article
- An Informatics-based Approach to Identify Key Pharmacological Components in Drug-Drug Interactions.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2020Article
- Pharmacogenetics of Methadone Response.Molecular diagnosis & therapy · 2018Review
- Complications with oxycodone and naloxone.Australian prescriber · 2017Article
- Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.Journal of molecular neuroscience : MN · 2014Article
- 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
- Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients.British journal of clinical pharmacology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects.
methodsTen methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide.
resultsThe urinary metabolic ratio for O-demethylation was significantly higher (P= 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P < 0.0002), but there was no significant difference (P= 0.36) in N-demethylation. Similar changes in plasma metabolic ratios were also found. In plasma, compared with those maintained on buprenorphine, the methadone-maintained subjects had increased codeine and norcodeine concentrations (P < 0.004), similar morphine (P= 0.72) and lower morphine-3- and -6- and codeine-6-glucuronide concentrations (P < 0.008).
conclusionMethadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6.
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