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Metabolism of Nicotine in Smokers and Nonsmokers

  • D. W. Sepkovic
  • N. J. Haley
Part of the Advances in Behavioral Biology book series (ABBI, volume 31)

Abstract

While a number of secondary reinforcers may exert some influence on cigarette smoking behavior, the major factor responsible for tobacco habituation is believed to be nicotine. Two studies on the metabolism of the N-oxidative metabolites have revealed substantial in vivo reduction of these compounds to nicotine after their chronic and subchronic administration to rats. Nicotine-N,N’-dioxide was also shown to be back-reduced to the parent alkaloid as evidenced by high levels of nicotine and cotinine in the plasma and urine of treated rats. In another study, the rate of elimination of cotinine in smokers and passively exposed nonsmokers was measured. Ten smokers quit smoking and the elimination of cotinine in plasma and urine was measured for eight days after cessation. Four nonsmokers were exposed to a sidestream smoke-polluted environment and the rate of cotinine disappearance was assessed. Cotinine elimination in the plasma of the passively exposed nonsmokers took at least twice as long as that of chronic cigarette smokers. The rate of elimination from the urine was also significantly slower in nonsmokers when compared with smokers. A new nicotine delivery method, a nicotine aerosol rod, was examined under standard FTC machine smoking conditions. In a pilot study, the uptake of nicotine from this nicotine aerosol rod was also measured in smokers and nonsmokers. The results indicated that per puff deliveries of nicotine were too small to be assessed by radioimmunoassay and that this method of nicotine delivery did not result in smoker satisfaction. More work is necessary if alternate methods of nicotine delivery are to be accepted by the population which continues to smoke.

Keywords

Urinary Cotinine Cotinine Concentration Nicotine Delivery Mainstream Smoke Smoking Mother 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hopkins, R, Wood, LW and Sinclair, NM: Evaluation of methods to estimate cigareete smoke uptake. Clin. Pharmacol. Ther. 36:788–794, 1984.PubMedCrossRefGoogle Scholar
  2. 2.
    Hoffmann, D, Haley, NJ, Adams, JD and Brunnemann, KD: Tobacco sidestream smoke: Uptake by nonsmokers. Prev. Med. 13:608–617, 1984.PubMedCrossRefGoogle Scholar
  3. 3.
    Etzel, RA, Greenberg, RA, Haley, NJ and Loda, FA. Urinary cotinine excretion in neonates exposed to tobacco smoke products in utero. J. Pediatr. 107:146–148, 1985.PubMedCrossRefGoogle Scholar
  4. 4.
    Ashton, H, Stepney, T, Teleford, R and Thompson, JW: Cardiovascular and behavioral responses to smoking. In (ed.) Greenhalgh, RM, Smoking and Arterial Disease, Pitman Medical Press, London, 1981, p. 258.Google Scholar
  5. 5.
    Isaac, PF and Rand, MJ: Cigarette smoking and plasma levels of nicotine. Nature 236:308, 1972.PubMedCrossRefGoogle Scholar
  6. 6.
    Hill, P and Marquardt, H: Plasma and urine changes after smoking different brands of cigarettes. Clin. Pharmacol. 27:652–655, 1980.Google Scholar
  7. 7.
    Sepkovic, DW, Haley, NJ: Biomedical applications of cotinine concentrations in biological fluids. Am. J. Public Health 75:663–664, 1985.PubMedCrossRefGoogle Scholar
  8. 8.
    McKennis, H, Turnbull, LB, Bowman, ER: L-(3-pyridyl) 7-methyl-amino-butyric acid as a urinary metabolite of nicotine. J. Am. Chem. Soc. 79:6342, 1957.CrossRefGoogle Scholar
  9. 9.
    Gorrod, JW and Jenner, P: The metabolism of tobacco alkaloids. Essays Toxicol. 6:35–78, 1975.Google Scholar
  10. 10.
    Gorrod, JW, Jenner, P, Keysell, GR and Mikhael, BR: Oxidative metabolism of nicotine by cigarette smokers with cancer of the urinary bladder. J. Natl. Cancer Inst. 52:1421–1424, 1974.PubMedGoogle Scholar
  11. 11.
    Booth, J and Boyland, E: The metabolism of nicotine into two optically-active stereoisomers of nicotine-l’-oxide by animal tissues in vitro and by cigarette smokers. Biochem. Pharmacol. 19:733–742,1970.PubMedCrossRefGoogle Scholar
  12. 12.
    Booth, J and Boyland, E: Enzymatic oxidation of (-) nicotine by guinea pig tissue in vitro. Biochem. Pharmacol. 20:407–412, 1971.PubMedCrossRefGoogle Scholar
  13. 13.
    Dajani, RM, Gorrod, JW and Beckett, AH: Hepatic and extrahepatic reduction of nicotine-l’-N-oxide in rats. Biochem. J. 130:88, 1972.Google Scholar
  14. 14.
    Klemish, HJ and Stadler, L: Untersuchungen Zur Bildung Von N’-nitroso-nornikotin auc nikotin-N’-oxid. Talanta 23:614–616, 1979.CrossRefGoogle Scholar
  15. 15.
    Sepkovic, DW, Haley, NJ, Axelrad, CM and LaVoie, EJ: Thyroid hormone concentrations in rats after chronic nicotine metabolite administration. Proc. Soc. Exp. Biol. Med. 177:412–416, 1984.PubMedGoogle Scholar
  16. 16.
    Sepkovic, DW, Haley, NJ, Axelrad, CM, Shigematsu, A and LaVoie, EJ: Short-term studies on the in vivo metabolism of N’-oxides of nicotine in rats. J. Toxicol. Environ. Health 18:205–214, 1986.PubMedCrossRefGoogle Scholar
  17. 17.
    Hoffmann, D and Adams, JD: Carcinogenic tobacco-specific N-nitrosamines in snuff and in the saliva of snuff dippers. Cancer Res. 41:4305–4308, 1981.PubMedGoogle Scholar
  18. 18.
    Hoffmann, D, LaVoie, EJ and Hecht, SS: Nicotine: A precursor for carcinogens. Cancer Lett. 26:67–75, 1985.PubMedCrossRefGoogle Scholar
  19. 19.
    Klein, AE and Gorrod, JW: Age as a factor in the metabolism of nicotine. Eur. J. Drug Metab. Pharmacokinet. 1:51–58, 1978.CrossRefGoogle Scholar
  20. 20.
    Correa, P, Pickle, LW, Fontham, L, Lin T and Haenszel W: Passive smoking and lung cancer. Lancet 2:595–597, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Hirayama, T: Passive smoking and lung cancer: Consistency of association. Lancet 2:1425–1426, 1983.PubMedCrossRefGoogle Scholar
  22. 22.
    Garfinkel, L, Auerbach, O and Joubert, L: Involuntary smoking and lung cancer: a case control study. J. Natl. Cancer Inst. 75:463–469, 1985.PubMedGoogle Scholar
  23. 23.
    Preston-Martin S, Yu MC, Benton B, Henderson, BE: N-Nitroso compounds and childhood brain tumors: a case control study, Cancer Res. 42:5240–5245, 1982.PubMedGoogle Scholar
  24. 24.
    Hoffmann, D, Haley, NJ, Brunnemann, KD, Adams, JD and Wynder, EL: Cigarette Sidestream Smoke: Formation analysis and model studies on the uptake by nonsmokers. U.S., Japan Meeting “New Etiology of Lung Cancer,” Honolulu, Hawaii, March 21–23, 1983.Google Scholar
  25. 25.
    Sepkovic DW, Haley, NJ, Hoffmann D. Elimination from the body of tobacco products by smokers and passive smokers. J. Amer. Med. Assoc. 256:863, 1986.CrossRefGoogle Scholar
  26. 26.
    Hoffmann, D, Haley, NJ, Adams, JD and Brunnemann, KD: Tobacco sidestream smoke: uptake by nonsmokers. Prev. Med. 13:608–617, 1984.PubMedCrossRefGoogle Scholar
  27. 27.
    Repace, JL and Lowrey, AH: A quantitative estimate of nonsmokers lung cancer risk from passive smoking. Environ. Int. 11:3–22, 1985.CrossRefGoogle Scholar
  28. 28.
    Hoffmann, D and Hecht, SS: Nicotine-derived N-nitrosamines and tobacco-related cancer: current status and future directions. Cancer Res. 45:935–944, 1985.PubMedGoogle Scholar
  29. 29.
    Greenberg, RA, Haley, NJ, Etzel, RA and Loda, FA: Nicotine and cotinine in urine and saliva. New Engl. J. Med. 310:1075, 1984.PubMedCrossRefGoogle Scholar
  30. 30.
    Luck, W and Heinz, N: Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers. J. Pediat. 107:816–820, 1985.PubMedCrossRefGoogle Scholar
  31. 31.
    U.S. Department of Health and Human Services, 1984. The Health Consequences of Smoking: Chronic Obstructive Lung Disease. DHHS publication No. (PHS) 84-50205.Google Scholar
  32. 32.
    Sepkovic DW, Colosimo, SG, Axelrad, CM, Adams, JD, and Haley, NJ. The delivery and uptake of nicotine from an aerosol rod. Amer. J. Publ. Health 76:1343, 1986.CrossRefGoogle Scholar
  33. 33.
    Johnston, A and Woollard, RC: STRIPE: an interactive computer program for the analysis of drug pharmacokinetics. J. Pharmacol. Methods 9:193–199, 1983.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • D. W. Sepkovic
    • 1
  • N. J. Haley
    • 1
  1. 1.Division of Nutrition and Endocrinology Naylor Dana InstituteAmerican Health FoundationValhallaUSA

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