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The Effects of Age on Hepatic Drug Metabolism

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Drug Studies in the Elderly

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Abstract

Aging is a very complex process that is not completely understood. In the human life cycle, the growth-and-development phase ends near the age of 30 years and is followed by a gradual, often linear decline.1 Many physiological and biochemical changes occur with “normal” aging. In addition, concomitant pathological conditions, lifelong habits, and environmental exposure also contribute to the biological changes in the elderly. As a result, there are wide differences in the rates of deterioration of organs and enzyme systems with age. Therefore, chronological aging may not necessarily be a true reflection of physiological aging.

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References

  1. Andres R: Physiological factors of aging significant to the clinician (summary of remarks).J Am Geriatr Soc 1969; 17: 274–277.

    PubMed  CAS  Google Scholar 

  2. Calloway NO, Foley CF, Lagerbloom P: Uncertainties in geriatric data. II. Organ size. J Am Geriatr Soc 1965; 13: 20–28.

    PubMed  CAS  Google Scholar 

  3. Geokas MC, Haverback BJ: The aging gastrointestinal tract. AmJ Surg 1969; 117: 881–892.

    Article  CAS  Google Scholar 

  4. Swift CG, Homeida M, Halliwell M, et al: Antipyrine disposition and liver size in the elderly. Eur J Clin Pharmacol 1978; 14: 149–152.

    Article  PubMed  CAS  Google Scholar 

  5. Bach B, Hansen JM, Kampmann JP, et al: Disposition of antipyrine and phenytoin correlated with age and liver volume in man. Clin Pharmacokinet 1981; 6: 389–396.

    Article  PubMed  CAS  Google Scholar 

  6. Wood AJJ, Vestal RE, Wilkinson GR, et al: Effect of aging and cigarette smoking on antipyrine and indocyanine green elimination. Clin Pharmacol Ther 1979; 26: 16–20.

    PubMed  CAS  Google Scholar 

  7. Gibaldi M, Perrier D: Pharmacokinetics, ed 2. New York and Basel, Marcel Dekker, Inc., 1982.

    Google Scholar 

  8. Wilkinson GR, Shand DG: A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975; 18: 377–390.

    PubMed  CAS  Google Scholar 

  9. Kornhauser DM, Wood AJJ, Vestal RE, et al: Biological determinants of propranolol disposition in man. Clin Pharmacol Ther 1978; 23: 165–174.

    PubMed  CAS  Google Scholar 

  10. Alvan G, Piafsky K, Lind M, et al: Effect of pentobarbital on the disposition of alprenolol. Clin Pharmacol Ther 1977; 22: 316–321.

    PubMed  CAS  Google Scholar 

  11. Sherlock S, Bearn AG, Billing BH, et al: Splanchnic blood flow in man by the bromsulpthalein method: the relation of peripheral plasma bromsulpthalein level to the calculated flow. J Lab Clin Med 1950; 35: 923–937.

    PubMed  CAS  Google Scholar 

  12. Bender AD: The effect of increasing age on the distribution of peripheral blood flow in man. J Am Geriatr Soc 1965; 13: 192–198.

    PubMed  CAS  Google Scholar 

  13. Rodeheffer RJ, Gerstenblith G, Becker LC, et al: Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 1984; 69: 203–213.

    Article  PubMed  CAS  Google Scholar 

  14. Vestal RE, Wood AJJ, Branch RA, et al: Effect of age and cigarette smoking on propranolol disposition. Clin Pharmacol Ther 1979; 26: 8–15.

    PubMed  CAS  Google Scholar 

  15. Farah F, Taylor W, Rawlins MD, et al: Hepatic drug acetylation and oxidation: Effects of aging in man. Br Med J 1977; 2: 155–156.

    Article  PubMed  CAS  Google Scholar 

  16. Vestal RE, McGuire EA, Tobin JD, et al: Aging and ethanol metabolism. Clin Pharmacol Ther 1977; 21: 343–354.

    PubMed  CAS  Google Scholar 

  17. Triggs, EJ, Nation RL, Long A, et al: Pharmacokinetics in the elderly. Eur J Clin Pharmacol 1975; 8: 55–62.

    Article  PubMed  CAS  Google Scholar 

  18. Shull HJ, Wilkinson GR, Johnson R, et al: Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 1976; 84: 420–425.

    PubMed  CAS  Google Scholar 

  19. Kraus JW, Desmond PV, Marshall JP, et al: Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 1978; 24: 411–419.

    PubMed  CAS  Google Scholar 

  20. O’Malley K, Crooks J, Duke E, et al: Effect of age and sex on human drug metabolism. Br Med J 1971; 3: 607–609.

    Article  PubMed  Google Scholar 

  21. Crooks J, O’Malley, K, Stevenson IH: Pharmacokinetics in the elderly. Clin Pharmacokinet 1976; 1: 280–296.

    Article  PubMed  CAS  Google Scholar 

  22. Vestal RE, Norris AH, Tobin JD, et al: Antipyrine metabolism in man: Influence of age, alcohol, caffeine, and smoking. Clin Pharmacol Ther 1975; 18: 425–432.

    PubMed  CAS  Google Scholar 

  23. Hart P, Farrell GC, Cooksley WGE, et al: Enhanced drug metabolism in cigarette smokers. Br Med J 1976; 2: 147–149.

    Article  PubMed  CAS  Google Scholar 

  24. Jusko WJ: Role of tobacco smoking in pharmacokinetics. J Pharmacokinet Biopharm 1978; 6: 7–39.

    Article  PubMed  CAS  Google Scholar 

  25. Gardner SK, Cady WJ, Ong YS: Effect of smoking on the elimination of propranolol hydrochloride. Int J Clin Pharmacol Ther Toxicol 1980; 18: 421–424.

    PubMed  CAS  Google Scholar 

  26. Twum-Barima Y, Finnigan T, Habash AI, et al: Impaired enzyme induction by rifampicin in the elderly. BrJ Clin Pharmacol 1984; 17: 595–596.

    CAS  Google Scholar 

  27. Salem SAM, Rajjayabun P, Shepherd AMM, et al: Reduced induction of drug metabolism in the elderly. Age Aging 1978; 7: 68–73.

    Article  CAS  Google Scholar 

  28. Mucklow JC, Fraser HS: The effects of age and smoking upon antipyrine metabolism. BrJ Clin Pharmacol 1980; 9: 613–614.

    CAS  Google Scholar 

  29. Cusack B, Kelly JG, Lavan J, et al: Theophylline kinetics in relation to age: The importance of smoking BrJ Clin Pharmacol 1980; 10: 109–114.

    CAS  Google Scholar 

  30. Pearson MW, Roberts CJC: Drug induction of hepatic enzymes in the elderly. Age Aging 1984; 13: 313–316.

    Article  CAS  Google Scholar 

  31. Cammarata RJ, Rodnan GP, Fennell RH: Serum anti-gamma globulin and antinuclear factors in the aged. J AMA 1967; 199: 115–118.

    Google Scholar 

  32. Greenblatt DJ: Reduced serum albumin concentration in the elderly: A report from the Boston Collaborative Drug Serveillance Program. J Am Geriatr Soc 1979; 27: 20–22.

    PubMed  CAS  Google Scholar 

  33. Bendayan R, Pieper JA, Stewart RB, et al: Influence of age on serum protein binding of propranolol. Eur J Clin Pharmacol 1984; 26: 251–254.

    Article  PubMed  CAS  Google Scholar 

  34. Adir J, Miller AK, Vestal RE: Effects of total plasma concentration and age on tolbutamide plasma protein binding. Clin Pharmacol Ther 1982; 31: 488–493.

    Article  PubMed  CAS  Google Scholar 

  35. Verbeeck RK, Cardinal JA, Wallace SM: Effect of age and sex on the plasma binding of acidic and basic drugs. Eur J Clin Pharmacol 1984; 27: 91–97.

    PubMed  CAS  Google Scholar 

  36. Patterson M, Heazelwood R, Smithurst B, et al: Plasma protein binding of phenytoin in the aged: In vivo studies. Br J Clin Pharmacol 1982; 13: 423–425.

    PubMed  CAS  Google Scholar 

  37. Gersovitz M, Munro HN, Udall J, et al: Albumin synthesis in young and elderly subjects using a new stable isotope methodology: response to level of protein intake. Metabolism 1980; 29: 1075–1086.

    Article  PubMed  CAS  Google Scholar 

  38. Tinguely D, Baumann P, Conti M, et al: Interindividual differences in the binding of antidepressives to plasma proteins: The role of the variants of alpha-l-acid glycoprotein. Eur J Clin Pharmacol 1985; 27: 611–666.

    Article  Google Scholar 

  39. Abernethy DR, Kerzner L: Age effects on alpha-l-acid glycoprotein concentration and imipramine plasma protein binding. J Am Geriatr Soc 1984; 32: 705–708.

    PubMed  CAS  Google Scholar 

  40. Sager G, Hansteen V, Aakesson I, et al: Effect of heparin on serum binding of propranolol in the acute phase of myocardial infraction. Br J Clin Pharmacol 1981; 12: 613–620.

    PubMed  CAS  Google Scholar 

  41. Blaine PG, Mucklow JC, Rawlins MD, et al: Determinants of plasma alpha- 1-acid glycoprotein concentrations in health. Br J Clin Pharmacol 1981; 12: 275 p.

    Google Scholar 

  42. Piafsky KM, Borga O, Odar-Cederlof I, et al: Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of alpha-lacid glycoprotein. N Engl J Med 1978; 299: 1435–1439.

    Article  PubMed  CAS  Google Scholar 

  43. Abramson FP, Jenkins J, Ostchega Y: Effects of cancer and its treatments on plasma concentration of alpha- 1-acid glycoprotein and propranolol binding. Clin Pharmacol Ther 1982; 32: 659–663.

    Article  PubMed  CAS  Google Scholar 

  44. Routledge PA, Stargel WW, Wagner GS, et al: Increased alpha- 1-acid glycoprotein and lidocaine disposition in myocardial infarction. Ann Intern Med 1980; 93: 701–704.

    PubMed  CAS  Google Scholar 

  45. Edwards DJ, Lalka D, Cerra F, et al: Alpha- 1-acidglycoprotein concentration and protein binding in trauma. Clin Pharmacol Ther 1982; 31: 62–67.

    Article  PubMed  CAS  Google Scholar 

  46. Jagadessan V, Krishnaswamy K: Drug binding in the undernourished: a study of the binding of propranolol to alpha-l-acid glycoprotein. Eur J Clin Pharmacol 1985; 27: 657–659.

    Article  Google Scholar 

  47. Routledge PA, Shand DG, Barchowsky A, et al: Relationship between alpha- 1-acid glycoprotein and lidocaine disposition in myocardial infarction. Clin Pharmacol Ther 1981; 30: 154–157.

    Article  PubMed  CAS  Google Scholar 

  48. McGowan FX, Reiter MJ, Pritchett ELC, et al: Verapamil plasma binding: Relationship to alpha-l-acid glycoprotein and drug efficacy. Clin Pharmacol Ther 1983; 33: 485–490.

    Article  PubMed  CAS  Google Scholar 

  49. Vestal RE: Pharmacology and aging. J Am Geriatr Soc 1982; 30: 191–200.

    PubMed  CAS  Google Scholar 

  50. Rowe JW, Troen BR: Sympathetic nervous system and aging in man. Endocr Rev 1980; 1: 167–179.

    Article  PubMed  CAS  Google Scholar 

  51. Rowe JW: Clinical research on aging: Strategies and directions. N Engl J Med 1977; 297: 1332–1336.

    Article  PubMed  Google Scholar 

  52. Vestal RE: Methodological problems associated with studies of drug metabolism in the elderly, in Turner P (ed): Clinial Pharmacology and Therapeutics: Proceedings of the First World Conference. London, MacMillan Publisher Ltd, 1980, pp 108–116.

    Google Scholar 

  53. Castleden CM, Kayne CM, Parsons RL: The effect of age on plasma levels of propranolol and practolol in man. Br J Clin Pharmacol 1975; 2: 303–306.

    PubMed  CAS  Google Scholar 

  54. Castleden CM, George CF: The effect of aging on the hepatic clearance of propranolol. Br J Clin Pharmacol 1979; 7: 49–54.

    PubMed  CAS  Google Scholar 

  55. Schneck DW, Luderer JR, Pritchard JF, et al: A comparison of the intrinsic clearance of propranolol in young and elderly subjects. Clin Pharmacol Ther 1980; 27: 284–285.

    Article  Google Scholar 

  56. Vestal RE, Dawson G: Pharmacology and aging, in Finch CE (ed): Handbook of the Biology of Aging, ed. 2. New York, Van Nostrand, 1985, pp 744–819.

    Google Scholar 

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Author information

Authors and Affiliations

  1. College of Pharmacy, Idaho State University, Pocatello, Idaho, 83209, USA

    Cho-Ming Loi

  2. Clinical Pharmacology and Gerontology Unit, Veterans Administration Medical Center, Boise, Idaho, 83702, USA

    Cho-Ming Loi & Robert E. Vestal

  3. Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, 98195, USA

    Robert E. Vestal

Authors
  1. Cho-Ming Loi
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  2. Robert E. Vestal
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Editor information

Editors and Affiliations

  1. Department of Geriatrics Cedars-Sinai Medical Center, University of California-Los Angeles School of Medicine, 90048, Los Angeles, California, USA

    Neal R. Cutler M.D. (Director) (Director)

  2. Clinical Pharmacokinetics Research Laboratory Pharmacy Department Clinical Center, National Institutes of Health, 20892, Bethesda, Maryland, USA

    Prem K. Narang Ph.D. (Supervisor) (Supervisor)

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© 1986 Plenum Publishing Corporation

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Loi, CM., Vestal, R.E. (1986). The Effects of Age on Hepatic Drug Metabolism. In: Cutler, N.R., Narang, P.K. (eds) Drug Studies in the Elderly. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1253-6_6

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  • DOI: https://doi.org/10.1007/978-1-4684-1253-6_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-1255-0

  • Online ISBN: 978-1-4684-1253-6

  • eBook Packages: Springer Book Archive

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