ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2015
Nicotine metabolite ratio (3-hydroxycotinine/cotinine) in plasma and urine by different analytical methods and laboratories: implications for clinical implementation.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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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.
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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
59 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.Molecular psychiatry · 2021Pooled it
- Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.Scientific reports · 2016Pooled it
- Do lab-based assessments of pretreatment smoking reinforcement and cue-specific craving predict smoking cessation with varenicline?Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2025Trial
- Evaluating mediators of the effect of varenicline preloading on smoking abstinence in a randomized controlled trial.Addiction (Abingdon, England) · 2025Trial
- Effects of open-label transdermal nicotine antidepressant augmentation on affective symptoms and executive function in late-life depression.Journal of affective disorders · 2024Trial
- Relationships Between the Nicotine Metabolite Ratio and Laboratory Assessments of Smoking Reinforcement and Craving Among Adults in a Smoking Cessation Trial.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Trial
- A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa.International journal of environmental research and public health · 2023Trial
- Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial.JAMA network open · 2022Trial
- Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder.The American journal on addictions · 2021Trial
- Evaluating the effect of switching to non-menthol cigarettes among current menthol smokers: an empirical study of a potential ban of characterising menthol flavour in cigarettes.Tobacco control · 2020Trial
- Impact of early nausea on varenicline adherence and smoking cessation.Addiction (Abingdon, England) · 2020Trial
- Pregnancy-Induced Increases in the Nicotine Metabolite Ratio: Examining Changes During Antepartum and Postpartum.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Trial
- Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes.Drug and alcohol dependence · 2018Trial
- Association of Reduced Nicotine Content Cigarettes With Smoking Behaviors and Biomarkers of Exposure Among Slow and Fast Nicotine Metabolizers: A Nonrandomized Clinical Trial.JAMA network open · 2018Trial
- Nicotine metabolites generate craniofacial defects that are worsened by ethanol exposure.PNAS nexus · 2026Article
- Rate of nicotine metabolism on risk of myocardial infarction among people with HIV who smoke cigarettes.PloS one · 2026Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program.Drug and alcohol dependence reports · 2024Article
- Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz-Based Therapy in People With HIV Who Smoke.Clinical pharmacology and therapeutics · 2024Article
- Simultaneous Measurement and Distribution Analysis of Urinary Nicotine, Cotinine, Trans-3'-Hydroxycotinine, Nornicotine, Anabasine, and Total Nicotine Equivalents in a Large Korean Population.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundThe highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3'-hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers.
methodsPlasma (n = 35) and urine (n = 35) samples were sent to eight different laboratories, which used similar and different methods of COT and 3HC measurements to derive the NMR. We used Bland-Altman analysis to assess agreement, and Pearson correlations to evaluate associations, between NMR measured by different methods.
resultsMeasures of plasma NMR were in strong agreement between methods according to Bland-Altman analysis (ratios, 0.82-1.16) and were highly correlated (all Pearson r > 0.96, P < 0.0001). Measures of urinary NMR were in relatively weaker agreement (ratios 0.62-1.71) and less strongly correlated (Pearson r values of 0.66-0.98, P < 0.0001) between different methods. Plasma and urinary COT and 3HC concentrations, while weaker than NMR, also showed good agreement in plasma, which was better than that in urine, as was observed for NMR.
conclusionsPlasma is a very reliable biologic source for the determination of NMR, robust to differences in these analytical protocols or assessment site. IMPACT: Together this indicates a reduced need for differential interpretation of plasma NMR results based on the approach used, allowing for direct comparison of different studies.
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