Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jun;17(6):1396-400.
doi: 10.1158/1055-9965.EPI-08-0242.

Stability of the nicotine metabolite ratio in ad libitum and reducing smokers

Marc E Mooney  1 , Zhong-Ze Li, Sharon E Murphy, Paul R Pentel, Chap Le, Dorothy K Hatsukami
Affiliations

Stability of the nicotine metabolite ratio in ad libitum and reducing smokers

Marc E Mooney et al. Cancer Epidemiol Biomarkers Prev. 2008 Jun.

Abstract

Background: The ratio of two nicotine metabolites, cotinine and trans-3'-hydroxycotinine (3-HC), has been validated as a method of phenotyping the activity of the liver enzyme cytochrome P450 (CYP) 2A6 and, thus, the rate of nicotine metabolism. Our objective was to evaluate the correlates and stability of the 3-HC to cotinine ratio in ad libitum and reducing smokers, using nicotine replacement therapy (NRT), over a period of months.

Methods: Smokers (n = 123, 94% Caucasian) participated in a smoking reduction study, where one-third of the sample smoked ad libitum for 8 weeks (Waitlist phase), before joining the rest of the participants for 12 weeks of cigarette reduction (Reduction phase) using NRT. Urinary nicotine, cotinine, and 3-HC were measured at each visit.

Results: The baseline 3-HC to cotinine ratio was significantly but weakly correlated with cigarettes per day (r = 0.19), BMI (r = -0.27), and waking at night to smoke (r = 0.23). As assessed by repeated measure ANOVA, the 3-HC to cotinine ratio was stable in the Waitlist phase [coefficient of variation for 3 to 4 measurements, 38% (range, 5-110%)], whereas minor variation was noted in the Reduction phase [coefficient of variation for 3-5 measurements, 35% (range, 10-107%)].

Conclusions: In nonreducing ad libitum smokers, the 3-HC to cotinine ratio was generally stable, whereas during smoking reduction using NRT, some small variation was detected. Although the current findings are suggestive of the stability of the 3-HC to cotinine ratio in a predominantly Caucasian sample smoking freely or reducing smoking with NRT, additional research is needed in more diverse populations.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Temporal stability of the 3-HC:COT ratio in those in the Reduction phase (Plot A) and Waitlist phase (Plot B). Values are geometric means and 95% CIs, back transformed from log 3-HC:COT. *Week 4 significantly greater than Week 1.
Figure 1
Figure 1
Temporal stability of the 3-HC:COT ratio in those in the Reduction phase (Plot A) and Waitlist phase (Plot B). Values are geometric means and 95% CIs, back transformed from log 3-HC:COT. *Week 4 significantly greater than Week 1.
See this image and copyright information in PMC

References

    1. Malaiyandi V, Sellers EM, Tyndale RF. Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence. Clin Pharmacol Ther. 2005;77:145–58. - PubMed
    1. Benowitz NL, Herrera B, Jacob P., 3rd Mentholated cigarette smoking inhibits nicotine metabolism. J Pharmacol Exp Ther. 2004;310:1208–15. - PubMed
    1. Benowitz NL, Lessov-Schlaggar CN, Swan GE, Jacob P., 3rd Female sex and oral contraceptive use accelerate nicotine metabolism. Clin Pharmacol Ther. 2006;79:480–8. - PubMed
    1. Benowitz NL, Pomerleau OF, Pomerleau CS, Jacob P., 3rd Nicotine metabolite ratio as a predictor of cigarette consumption. Nicotine Tob Res. 2003;5:621–4. - PubMed
    1. Dempsey D, Tutka P, Jacob P, 3rd, et al. Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther. 2004;76:64–72. - PubMed

Publication types