Nicotine metabolite ratio: Comparison of the three urinary versions to the plasma version and nicotine clearance in three clinical studies

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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