Trial reportAnesthesiology2015
Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.
Trial report in Anesthesiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01648283 (Role of CYP2B6 Polymorphisms in Methadone Metabolism and Clearance), which is not on this map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Role of CYP2B6 Polymorphisms in Methadone Metabolism and Clearance
Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 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
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion.Drug metabolism and disposition: the biological fate of chemicals · 2024Trial
- Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients.Expert review of clinical pharmacology · 2019Trial
- Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.Anesthesia and analgesia · 2019Trial
- Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition.Clinical pharmacology and therapeutics · 2019Trial
- Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Bupropion as Treatment for Methadone-Emergent Sexual Dysfunction in Men.American journal of men's health · 2018Trial
- Effects of Genetic Polymorphisms of CYP2B6 on the Pharmacokinetics of Bupropion and Hydroxybupropion in Healthy Chinese Subjects.Medical science monitor : international medical journal of experimental and clinical research · 2018Trial
- Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease.Pediatric blood & cancer · 2016Trial
- Opioid Add-On Combination Therapy for Cancer Pain: Pharmacological Rationale, Clinical Evidence, and Future Directions.CNS drugs · 2026Review
- Whole exome sequencing analysis of suicidal thoughts and behaviors in a veteran cohort implicates inflammatory pathways and genes previously associated with psychiatric and neurodegenerative diseases.Journal of affective disorders · 2026Article
- Pharmacogenomic-guided opioid prescribing in hospice: reducing toxicity while maximizing symptom relief.Frontiers in medicine · 2026Review
- Pharmacometric modeling of opioid disposition in pregnancy: a systematic review of PopPK and PBPK approaches, model limitations, and future directions.Frontiers in pharmacology · 2026Review
- Mortality in methadone poisoning: a decade-long analysis of clinical predictors in an Iranian cohort.International journal of physiology, pathophysiology and pharmacology · 2026Article
- Association ofBalkan journal of medical genetics : BJMG · 2025Article
- The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Unveiling the heritability of selected unexplored pharmacogenetic markers in the Saudi population.Frontiers in pharmacology · 2025Article
- Drug-Drug Interaction Studies of Esmethadone (REL-1017) Involving CYP3A4- and CYP2D6-Mediated Metabolism.Drugs in R&D · 2024Article
- Fetal and Infant Effects of Maternal Opioid Use during Pregnancy: A Literature Review including Clinical, Toxicological, Pharmacogenomic, and Epigenetic Aspects for Forensic Evaluation.Children (Basel, Switzerland) · 2024Review
- Association between CYP2B6 genetic variability and cyclophosphamide therapy in pediatric patients with neuroblastoma.Scientific reports · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundInterindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone elimination. The CYP2B6 gene is highly polymorphic, with several variant alleles. CYP2B6.6, the protein encoded by the CYP2B6*6 polymorphism, deficiently catalyzes methadone metabolism in vitro. This investigation determined the influence of CYP2B6*6, and other allelic variants encountered, on methadone concentrations, clearance, and metabolism.
methodsHealthy volunteers in genotype cohorts CYP2B6*1/*1 (n = 21), CYP2B6*1/*6 (n = 20), and CYP2B6*6/*6 (n = 17), and also CYP2B6*1/*4 (n = 1), CYP2B6*4/*6 (n = 3), and CYP2B6*5/*5 (n = 2) subjects, received single doses of IV and oral methadone. Plasma and urine methadone and metabolite concentrations were determined by tandem mass spectrometry.
resultsAverage S-methadone apparent oral clearance was 35 and 45% lower in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively, compared with CYP2B6*1/*1. R-methadone apparent oral clearance was 25 and 35% lower in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively, compared with CYP2B6*1/*1. R- and S-methadone apparent oral clearance was threefold and fourfold greater in CYP2B6*4 carriers. IV and oral R- and S-methadone metabolism was significantly lower in CYP2B6*6 carriers compared with that of CYP2B6*1 homozygotes and greater in CYP2B6*4 carriers. Methadone metabolism and clearance were lower in African Americans in part because of the CYP2B6*6 genetic polymorphism.
conclusionsCYP2B6 polymorphisms influence methadone plasma concentrations, because of altered methadone metabolism and thus clearance. Genetic influence is greater for oral than IV methadone and S- than R-methadone. CYP2B6 pharmacogenetics explains, in part, interindividual variability in methadone elimination. CYP2B6 genetic effects on methadone metabolism and clearance may identify subjects at risk for methadone toxicity and drug interactions.
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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.