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Influence of Age and Smoking on Drug Kinetics in Man Studies Using Model Compounds

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Summary

The effect of advanced age on drug disposition and response is the subject of an increasing number of research studies. Cigarette smoking and other environmental factors have been shown to influence the metabolism of some drugs. Studies of the effect of age on the pharmacokinetics of antipyrine, indocyanine green and propranolol indicate that the association of increased drug metabolism and smoking occurs predominantly in the young and that apparent liver blood flow declines with age regardless of smoking habits. This age related effect of smoking on drug metabolism may reflect a reduced capacity for hepatic enzyme induction in the elderly. The relative importance of age related alterations in the intrinsic drug metabolising ability of the liver and in liver blood flow depend on the pharmacokinetic characteristics of the drug being investigated.

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References

  • Adelman, R.C.: Age-dependent effects of enzyme induction — A biochemical expression of aging. Experimental Gerontology 6: 75–87 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Bender, A.D.: The effect of increasing age on the distribution of peripheral blood flow in man. Journal of the American Geriatric Society 13: 192–198 (1965).

    CAS  Google Scholar 

  • Birnbaum, L.S. and Baird, M.B.: Induction of hepatic mixed function oxidases in senescent rodents. Experimental Gerontology 13: 229–303 (1978).

    Google Scholar 

  • Blaschke, T.F.: Protein binding and kinetics of drugs in liver diseases. Clinical Pharmacokinetics 2: 32–44 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Brandfonbrener, M.; Landowne, M. and Shock, N.: Changes in cardiac output with age. Circulation 12: 557–566 (1955).

    Article  PubMed  CAS  Google Scholar 

  • Castleden, C.M. and George, C.F.: The effect of ageing on the hepatic clearance of propranolol. British Journal of Clinical Pharmacology 7: 49–54 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Castleden, C.M.; Kayne, C.M. and Parsons, R.L.: The effect of age on plasma levels of propranolol and practolol in man. British Journal of Clinical Pharmacology 2: 303–306 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Conney, A.H.; Pantuck, E.J.; Hsiao, K.-C; Kuntzman, R.; Alvares, A.P. and Kappas, A.: Regulation of drug metabolism in man by environmental chemicals and diet. Federation Proceedings 36: 1647–1652 (1977).

    PubMed  CAS  Google Scholar 

  • Crooks, J.; Os’Malley, K. and Stevenson, I.H.: Pharmacokinetics in the elderly. Clinical Pharmacokinetics 1: 280–296 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Hart, P.; Farrell, G.C.; Cooksley, W.G.E. and Powell, L.W.: Enhanced drug metabolism in cigarette smokers. British Medical Journal 3: 147–149 (1976).

    Article  Google Scholar 

  • Jick, H.: Smoking and clinical drug effects. Medical Clinics of North America 58: 1143–1149 (1974).

    PubMed  CAS  Google Scholar 

  • Jusko, W.J.: Role of tobacco smoking in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 6: 7–39 (1978).

    PubMed  CAS  Google Scholar 

  • Kapitulnik, J.; Poppers, P.J. and Conney, A.J.: Comparative metabolism of benzo(a)pyrene and drugs in human liver. Clinical Pharmacology and Therapeutics 21: 166–176 (1977).

    PubMed  CAS  Google Scholar 

  • Kato, R. and Takanaka, A.: Metabolism of drugs in old rats. I. Activities of NADPH-linked electron transport and drug metabolizing enzyme systems in liver microsomes of old rats. Japanese Journal of Pharmacology 18: 381–388 (1968a).

    Article  PubMed  CAS  Google Scholar 

  • Kato, R. and Takanaka, A.: Effect of phenobarbital on electron transport system, oxidation and reduction of drugs in liver microsomes of rats of different ages. Journal of Biochemistry 63: 406–408 (1968b).

    PubMed  CAS  Google Scholar 

  • Lewis, G.P.; Jusko, W.J.; Coughlin, L.L. and Hartz, S.: Cadmium accumulation in man. Influence of smoking, occupation, alcoholic habit and disease. Journal of Chronic Diseases 25: 717–726 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Liddell, D.E.; Williams, F.M. and Briant, R.H.: Phenazone (antipyrine) metabolism and distribution in young and elderly adults. Clinical and Experimental Pharmacology and Physiology 2: 481–487 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Nebert, D.W.; Winker, J. and Gelboin, H.V.: Aryl hydrocarbon hydroxylase activity in human placenta from cigarette smoking and nonsmoking women. Cancer Research 29: 1763–1769 (1969).

    PubMed  CAS  Google Scholar 

  • Pelkonen, O.; Metabolism of benzo(a)pyrene in human adults and fetal tissues; in Freudenthal and Jones (Eds), Carcinogenesis, Vol. 1: Polynuclear Aromatic Hydrocarbons: Chemistry, Metabolism, and Carcinogenesis, pp. 9–12 (Raven Press, New York 1976).

    Google Scholar 

  • Os’Malley, K.; Crooks, J.; Duke, E. and Stevenson, I.H.: Effect of age and sex on human drug metabolism. British Medical Journal 3: 607–609 (1971).

    Article  Google Scholar 

  • Rasmussen, S.N.; Hansen, J.M.; Kampmann, J.P.; Skovstad, L. and Bach, B.: Drug metabolism in relation to liver volume and age (Abst). Scandinavian Journal of Gastroenterology 11: 86 (1976).

    Google Scholar 

  • Richey, D.P. and Bender, D.: Pharmacokinetic consequences of aging. Annual Review of Pharmacology and Toxicology 17: 49–65 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Rowe, J.W.: Clinical research on aging: Strategies and directions. New England Journal of Medicine 297: 1332–1336 (1977).

    Article  PubMed  Google Scholar 

  • Swift, C.G.; Homeida, M.; Halliwell, M. and Roberts, C.J.C.: Antipyrine disposition and liver size in the elderly. European Journal of Clinical Pharmacology 14: 149–152 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Triggs, E.J. and Nation, R.L.: Pharmacokinetics in the aged: A review. Journal of Pharmacokinetics and Biopharmaceutics 3: 387–418 (1975).

    PubMed  CAS  Google Scholar 

  • U.S. Department of Health, Education and Welfare: Smoking and Health-, A Report of the Surgeon General. DHEW Publication No. (PHS) 79-50066. Washington D.C. (1979), pp.12-1–12-91.

  • Vestal, R.E.: Aging and pharmacokinetics: Impact of altered physiology in the elderly; in Cherkin, Finch, Karash, Makinodan, Scott and Strehler (Eds) Physiology and Cell Biology of Aging (Aging, Volume 8) pp. 185–201, (Raven Press, New York 1979).

    Google Scholar 

  • Vestal, R.E.: Drug use in the elderly: A review of problems and special considerations. Drugs 16: 358–382 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Vestal, R.E.; Norris, A.H.; Tobin, J.D.; Cohen, B.H.; Shock, N.W. and Andres, R.: Antipyrine metabolism in man: Influence of age, alcohol, caffeine, and smoking. Clinical Pharmacology and Therapeutics 18: 425–432 (1975).

    PubMed  CAS  Google Scholar 

  • Vestal, R.E.; Wood, A.J.J.; Branch, R.A.; Shand, D.G. and Wilkinson, G.R.: Effects of age and cigarette smoking on the disposition of propranolol in man. Clinical Pharmacology and Therapeutics 26: 8–15 (1979).

    PubMed  CAS  Google Scholar 

  • Walle, T.; Conradi, E.C.; Walle, U.K.: Fagan, T.C. and Gaffney, T.C.: The predictable relationship between plasma levels and dose during chronic propranolol therapy. Clinical Pharmacology and Therapeutics 24: 668–677 (1978).

    PubMed  CAS  Google Scholar 

  • Welch, R.M.; Cavallito, J. and Gillespie, D.D.: Effects of analgesics and exposure to cigarette smoke on the metabolism of acetophenetidin by rat tissues. Drug Metabolism and Disposition 1: 211–215 (1973).

    PubMed  CAS  Google Scholar 

  • Welch, R.M.; Harrison, Y.E.; Conney, A.H.; Poppers, P.J. and Finster, M.: Cigarette smoking: Stimulatory effect on metabolism of 3,4-benzpyrene by enzymes in human placenta. Science 160: 541–542 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Welch, R.M.; Hughes, C.R. and De Angelis, R.L.: Effect of 3-methylcholantherene pretreatment on the bioavailability of phenacetin in the rat. Drug Metabolism and Disposition 4: 402–406 (1976).

    PubMed  CAS  Google Scholar 

  • Wilkinson, G.R. and Shand, D.G.: A physiological approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390 (1975).

    PubMed  CAS  Google Scholar 

  • Wilson, J.T.; Van Boxtel, C.J.; Alvan, G. and Sjoqvist, F.: Failure of vitamin C to affect the pharmacokinetic profile of anti-pyrine in man. Journal of Clinical Pharmacology 16: 265–270 (1976).

    PubMed  CAS  Google Scholar 

  • Wood, A.J.J.; Vestal, R.E.; Wilkinson, G.R.; Branch, R.A. and Shand, D.C.: Effects of aging and cigarette smoking on anti-pyrine and indocyanine green elimination. Clinical Pharmacology and Therapeutics 26: 16–20 (1979).

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA

    R. E. Vestal & A. J. J. Wood

  2. Research Service (151), Veterans Administration Medical Center, 5th and Fort Streets, Boise, Idaho, 83702, USA

    R. E. Vestal & A. J. J. Wood

  3. Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

    R. E. Vestal & A. J. J. Wood

Authors
  1. R. E. Vestal
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  2. A. J. J. Wood
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Vestal, R.E., Wood, A.J.J. Influence of Age and Smoking on Drug Kinetics in Man Studies Using Model Compounds. Clin Pharmacokinet 5, 309–319 (1980). https://doi.org/10.2165/00003088-198005040-00001

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