Relationship between cotinine and trans-3′-hydroxycotinine glucuronidation and the nicotine metabolite ratio in Caucasian smokers

Abstract Introduction Smokers who use opioids smoke more cigarettes per day (CPD) than non-opioid users, which could be due to the effects of opioids on nicotine metabolism. Moreover, nicotine metabolism increases during pregnancy, potentially making quitting more difficult for pregnant smokers. We examined nicotine metabolism and its association with opioid use (OU) and CPD in pregnant smokers. Methods We recruited pregnant women who smoked at least 5 CPD for a clinical trial of smoking cessation. Plasma nicotine metabolite ratio (NMR; trans-3′-hydroxycotinine (3HC)/cotinine)—a biomarker of nicotine metabolism—OU (involving methadone, buprenorphine, fentanyl, oxycodone, or tramadol), and CPD were assessed at baseline. We used linear regression to examine the associations between log-transformed NMR, OU, and CPD, adjusting for race/ethnicity and menthol smoking. Results Among 129 pregnant smokers, 25 (19%) were opioid users; most were maintained on methadone (n = 14). Compared to non-OU smokers, OU smokers had higher median CPD (10.0 vs. 7.0, p = .0007), serum 3HC (81.0 vs. 42.0 ng/mL, p = .0001), and NMR (0.63 vs. 0.43, p < .0001). In addition, methadone-maintained smokers had a higher median NMR than non-OU smokers (0.66 vs. 0.43, p = .0004). Adjusting for covariates, log-transformed NMR was greater in OU smokers (p = .012), specifically methadone-maintained smokers (p = .024), than non-OU smokers. Conclusions Our preliminary results show that OU is associated with a higher NMR in pregnant smokers. A larger study sample is needed to replicate this finding, examine potential mechanisms, and determine its clinical significance. Implications Among pregnant smokers, we observed that nicotine metabolism was significantly faster among opioid users—the majority of whom were on methadone maintenance—compared to nonusers, which could have implications for smoking cessation. Further studies are needed to replicate this finding, evaluate potential mechanisms, and determine its clinical significance.

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Stability of the Nicotine Metabolite Ratio in ad Libitum and Reducing Smokers

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-08-0242 ◽

2008 ◽

Vol 17 (6) ◽

pp. 1396-1400 ◽

Cited By ~ 28

Author(s):

M. E. Mooney ◽

Z.-z. Li ◽

S. E. Murphy ◽

P. R. Pentel ◽

C. Le ◽

...

Keyword(s):

Metabolite Ratio ◽

Ad Libitum ◽

Nicotine Metabolite Ratio

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The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study

10.1101/299834 ◽

2018 ◽

Cited By ~ 3

Author(s):

Amy E. Taylor ◽

Rebecca C. Richmond ◽

Teemu Palviainen ◽

Anu Loukola ◽

Jaakko Kaprio ◽

...

Keyword(s):

Body Mass Index ◽

Dna Methylation ◽

Body Mass ◽

Mendelian Randomization ◽

Causal Effect ◽

Smoking Initiation ◽

Smoking Behaviour ◽

Bidirectional Association ◽

Metabolite Ratio ◽

Nicotine Metabolite Ratio

AbstractBackgroundGiven clear evidence that smoking lowers weight, it is possible that individuals with higher body mass index (BMI) smoke in order to lose or maintain their weight.Methods and FindingsWe undertook Mendelian randomization analyses using 97 genetic variants associated with BMI. We performed two sample Mendelian randomization analyses of the effects of BMI on smoking behaviour in UK Biobank (N=335,921) and the Tobacco and Genetics consortium genomewide association study (GWAS) (N≤74,035) respectively, and two sample Mendelian randomization analyses of the effects of BMI on cotinine levels (N≤4,548) and nicotine metabolite ratio (N≤1,518) in published GWAS, and smoking-related DNA methylation in the Avon Longitudinal Study of Parents and Children (N≤846).In inverse variance weighted Mendelian randomization analysis, there was evidence that higher BMI was causally associated with smoking initiation (OR for ever vs never smoking per one SD increase in BMI: 1.19, 95% CI: 1.11 to 1.27) and smoking heaviness (1.45 additional cigarettes smoked per day per SD increase in BMI, 95% CI: 1.03 to 1.86), but little evidence for a causal effect with smoking cessation. Results were broadly similar using pleiotropy robust methods (MR-Egger, median and weighted mode regression). These results were supported by evidence for a causal effect of BMI on DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus. There was no strong evidence that BMI was causally associated with cotinine, but suggestive evidence for a causal negative association with the nicotine metabolite ratio.ConclusionsThere is a causal bidirectional association between BMI and smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism. It may be useful to consider BMI and smoking together when designing prevention strategies to minimise the effects of these risk factors on health outcomes.

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Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance

Pharmacogenetics and Genomics ◽

10.1097/fpc.0000000000000427 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Evangelia Liakoni ◽

Rachel F. Tyndale ◽

Peyton Jacob ◽

Delia A. Dempsey ◽

Newton Addo ◽

...

Keyword(s):

Metabolite Ratio ◽

The Relationship ◽

Nicotine Metabolite Ratio

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Correlates of the nicotine metabolite ratio in Alaska Native people who smoke cigarettes.

Experimental and Clinical Psychopharmacology ◽

10.1037/pha0000461 ◽

2021 ◽

Author(s):

Erin A. Vogel ◽

Neal L. Benowitz ◽

Jordan Skan ◽

Matthew Schnellbaecher ◽

Judith J. Prochaska

Keyword(s):

Alaska Native ◽

Native People ◽

Metabolite Ratio ◽

Nicotine Metabolite Ratio

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Characteristics of smokers according to their Nicotine Metabolite Ratio, preliminary results from a real-life experience

10.1183/1393003.congress-2017.pa4479 ◽

2017 ◽

Author(s):

Gianfranco Puppo ◽

Francesco Pistelli ◽

Stefano Fogli ◽

Marco Lazzeretti ◽

Ferruccio Aquilini ◽

...

Keyword(s):

Life Experience ◽

Real Life ◽

Preliminary Results ◽

Metabolite Ratio ◽

Nicotine Metabolite Ratio

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Rapid Nicotine Metabolite Ratio and Successful Quitting: Acceptable Explanation

Nicotine & Tobacco Research ◽

10.1093/ntr/ntx188 ◽

2017 ◽

Vol 20 (7) ◽

pp. 908-908 ◽

Cited By ~ 1

Author(s):

Tomoyuki Kawada

Keyword(s):

Metabolite Ratio ◽

Nicotine Metabolite Ratio

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Creating a Personalized Smoking Cessation Pharmacotherapy Program in Smokers with Crohn's Disease Utilizing Nicotine Metabolite Ratio (NMR)

Gastroenterology ◽

10.1016/s0016-5085(17)30660-1 ◽

2017 ◽

Vol 152 (5) ◽

pp. S93

Author(s):

Elizabeth A. Scoville ◽

Quinn Wells ◽

Shannon C. Peyton ◽

Sara N. Horst ◽

David A. Schwartz ◽

...

Keyword(s):

Smoking Cessation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Metabolite Ratio ◽

Nicotine Metabolite Ratio

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Nicotine metabolite ratio and smoking outcomes using nicotine replacement therapy and varenicline among smokers with and without psychiatric illness

Journal of Psychopharmacology ◽

10.1177/0269881118773532 ◽

2018 ◽

Vol 32 (9) ◽

pp. 979-985

Author(s):

Matthew Clyde ◽

Andrew Pipe ◽

Charl Els ◽

Robert Reid ◽

Angel Fu ◽

...

Keyword(s):

Smoking Cessation ◽

Replacement Therapy ◽

Nicotine Replacement Therapy ◽

Odds Ratio ◽

Supporting Evidence ◽

Nicotine Replacement ◽

Psychiatric Status ◽

Metabolite Ratio ◽

Psychiatric Conditions ◽

Nicotine Metabolite Ratio

Introduction: It has been suggested that the effectiveness of nicotine replacement smoking cessation pharmacotherapy may be enhanced by assessing rates of nicotine metabolism using the nicotine metabolite ratio – which reflects differences in the activity of the CYP2A6 hepatic enzyme – and titrating doses appropriately. To date, supporting evidence is equivocal, with little information regarding the assessment and effectiveness of the nicotine metabolite ratio among smokers with psychiatric conditions. Methods: The nicotine metabolite ratio of 499 smokers from the FLEX trial was determined using urine samples obtained at baseline. They were randomized to receive either: standard transdermal nicotine (nicotine replacement therapy); extended nicotine replacement therapy + adjunct nicotine agent; or varenicline. Primary cessation outcomes were seven-day point prevalence at 5, 10, 22, and 52 weeks post-target quit date, comparing across treatment and psychiatric status. Our principal analysis employed logistic regression (outcome: abstinence), using slow metabolizers as the reference category. Results: No differences were observed by nicotine metabolite ratio classification (slow, moderate, fast) with respect to any demographic or smoking-related variables. Nicotine metabolite ratio class did not predict smoking cessation in either the overall sample, or by treatment condition at any time-point (week 52 moderate metabolizers: odds ratio 1.34, 95% confidence interval (0.68–2.63), p=0.394; fast metabolizers: odds ratio 1.04 (0.56–1.91), p=0. 906). Conclusion: Our results did not find any associations between nicotine metabolite ratio and cessation outcomes among smokers using nicotine replacement therapy or varenicline with and without lifetime psychiatric conditions.

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