Literature DB >> 15735610

Influence of menstrual cycle on cytochrome P450 2A6 activity and cardiovascular effects of nicotine.

Janne Hukkanen1, Steven G Gourlay, Saraswati Kenkare, Neal L Benowitz.   

Abstract

BACKGROUND AND OBJECTIVES: The phase of the menstrual cycle has been reported to affect frequency of smoking, withdrawal symptoms, and the likelihood of smoking cessation in women. Cytochrome P450 (CYP) 2A6 is primarily responsible for the metabolism of nicotine. Our objective was to evaluate the effect of the phase of the menstrual cycle on the activity of CYP2A6 and the cardiovascular effects of nicotine.
METHOD: Eleven healthy, nonsmoking women received a 30-minute combined infusion of deuterium-labeled nicotine and cotinine (0.5 microg . kg(-1) . min(-1) of each compound) during the midfollicular and midluteal phases of the menstrual cycle. Nicotine and cotinine pharmacokinetic parameters and plasma adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine responses were measured over time.
RESULTS: There were no biologically or statistically significant differences in the comparison of menstrual cycle phases with regard to the pharmacokinetics of nicotine and cotinine. Nicotine clearance was 1000 +/- 315 mL/min and 1047 +/- 271 mL/min in the follicular and luteal phases, respectively (geometric mean ratio, 1.06; 90% confidence interval, 0.87-1.29). Cotinine clearance was 44 +/- 20 mL/min and 55 +/- 42 mL/min in the follicular and luteal phases, respectively (geometric mean ratio, 1.13; 90% confidence interval, 0.90-1.41). Nicotine infusion increased blood pressure, heart rate, and epinephrine concentrations. There were no differences in catecholamine, ACTH, or hemodynamic responses to nicotine infusion between menstrual cycle phases, although norepinephrine concentrations were constantly higher in the luteal phase compared with the follicular phase.
CONCLUSIONS: CYP2A6 activity is not affected by menstrual cycle phase, and it is unlikely that menstrual cycle-related smoking habits of women are determined by changes in nicotine pharmacokinetics. The effects of nicotine on plasma ACTH and catecholamine levels and hemodynamic parameters are not altered by menstrual cycle phase in healthy, nonsmoking women.

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Year:  2005        PMID: 15735610     DOI: 10.1016/j.clpt.2004.10.012

Source DB:  PubMed          Journal:  Clin Pharmacol Ther        ISSN: 0009-9236            Impact factor:   6.875


  10 in total

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Authors:  Neal L Benowitz; Janne Hukkanen; Peyton Jacob
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4.  Subjective, physiological, and cognitive responses to intravenous nicotine: effects of sex and menstrual cycle phase.

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6.  Examining the Validity of Self-reported Primary and Secondary Exposure to Cigarette Smoke in Adolescent Girls: The Utility of Salivary Cotinine as a Biomarker.

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9.  Association of menstrual phase with smoking behavior, mood and menstrual phase-associated symptoms among young Japanese women smokers.

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10.  Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking.

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  10 in total

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