Geriatric Nephrology and Urology

, Volume 2, Issue 3, pp 155–167 | Cite as

Pharmacokinetics in the elderly

  • Pierre Veyssier
Review Article


The rapidly increasing proportion of persons over 65 years old is well known and is associated with a challenge for health care professionnels vis à vis the use of modern drug therapy, and a higher risk of adverse drug reactions. These reactions are often related to inappropriate therapy based on an incomplete knowledge of changes in drug handling in the elderly. Multiple disease, concomitant therapy, environmental conditions, social behaviour, compliance, changes in physiology with advancing age can all alter pharmacokinetics and pharmacodynamics of drugs. Age can modify drug absorption, metabolism, distribution and elimination. The changes associated with aging in drug interaction and the role of underlying clinical status are discussed. The pharmacokinetics of some drugs in the elderly are described. Careful attention to concomitant drug therapy for multiple disease is needed before prescribing for elderly patients.

Key words

Pharmacokinetics elderly 


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  1. 1.
    Dawling S, Grome P. Clinical pharmacokinetic considerations in the elderly. An update. Clin Pharmacokinet 1989; 17(4): 236–263.Google Scholar
  2. 2.
    Moore SR, Jones JK. Adverse drug reaction surveillance in the geriatric population: a preliminary view. In: Moore SR, Teal TW, editors. Geriatric drug use: clinical and social perspectives. New York: Pergamon Press, 1985: 70–77.Google Scholar
  3. 3.
    Tregaskis BF, Stevenson IH. Pharmacokinetics in old age. Brit M ed Bull 1990; 46: 9–21.Google Scholar
  4. 4.
    Owen JA, Sitar DS, Berger L, Brownell L, Duke PC, Mitenko PA. Age related morphine kinetics. Clin Pharmacol Ther 1983; 34: 364–368.Google Scholar
  5. 5.
    Greenblatt DJ, Allen MD, Harmatz JS. Diazepam disposition determinants. Clin Pharmacol Ther 1980; 27: 301–12.Google Scholar
  6. 6.
    Stewart RB, Caranasos GJ. Medical compliance in the elderly. Med Clin North Am 1989; 73(6): 1551–1563.Google Scholar
  7. 7.
    Ljunberg BI, Nilsson Ehle I. Pharmacokinetics of antimicrobial agents in elderly. Rev Infect Dis 1987; 9: 250–262.Google Scholar
  8. 8.
    Stevenson IH, Salem SAM, Shepherd AMM. Studies on drug absorption and metabolism in the elderly. In: Crooks J, Stevenson IH, editors. Drugs and the Elderly. Baltimore: University Park Press, 1979: 51–62.Google Scholar
  9. 9.
    Rossmann I. Clinical Geriatrics. 2nd ed. Philadelphia: J.B. Lippincott, 1979: 23-52, 132-7, 224–229.Google Scholar
  10. 10.
    Wallace SM, Verbeek RK. Plasma protein binding of drugs in the elderly. Clinical Pharmacokinet 1987; 12: 41–72Google Scholar
  11. 11.
    Wallace S, Whiting B, Runcie J. Factors affecting drug binding in plasma of elderly patients. Br J Clin Pharmacol 1976; 3: 327–330.Google Scholar
  12. 12.
    Bach B, Hansen JM, Kampman JP. Disposition of antipyrin and phenytoin correlated with age on liver volume in man. Clin Pharmacokinet 1961; 6: 389–396.Google Scholar
  13. 13.
    Salem SAM, Rajayabun P, Shepherd AMM. Reduced induction of drug metabolism in the elderly. Age Ageing 1978; 7: 68–73.Google Scholar
  14. 14.
    Epstein M. Effect of the aging on the kidney. Fed Proc 1979; 38: 168–72.Google Scholar
  15. 15.
    Lassman HB, Puri SK, Ho I, Salo R, Mezzino MJ. Pharmacokinetics of roxithromycin. J Clinic Pharmacol 1988; 28(2): 141–2.Google Scholar
  16. 16.
    Hirata CA, Guay DRP, Awni WM, Stein DJ, Peterson PK. Steady state pharmacokinetics of intravenous and oral ciprofloxacin in elderly patients. Antimicrob Agents Chemother 1989; 33: 1927–31.Google Scholar
  17. 17.
    Veyssier P, Darchis JP, Devillers A. Pharmacocinétique du cefuroxime axetil administré par voie orale chez le sujet âgé. Therapie 1988; 43: 355–9.Google Scholar
  18. 18.
    Irvine RE, Grove J, Toseland PA. Effect of age on the hydroxylation of amylobarbitone sodium in man. Br J Clin Pharmacol 1975; 2: 303–6.Google Scholar
  19. 19.
    Garattini S, Marcucci F, Marselli PL. The significance of measuring blood levels of benzodiazepines. In: Davies DS, Pritchard BNC, editors. Biological effects of drugs in relation to their plasma concentration. Baltimore: University Park Press, 1973: 211–25.Google Scholar
  20. 20.
    Blanchine JR, Calimlin LR, Morgan JP, Dujuvne CA, Lasagna L. Metabolism and absorption of L 3, 4 dihydroxyphenyl alanine in patients with Parkinson's disease. Am NY Acad Sci 1971; 179: 126–40.Google Scholar
  21. 21.
    Castledon CM, George CF. The effect of aging on the hepatic clearance of propranolol. Br J Pharmacol 1979; 7:49–54.Google Scholar
  22. 22.
    Cohen JL. Pharmacokinetic changes in aging. Am J Med 1986; 80 Suppl. 5A: 31–8.Google Scholar
  23. 23.
    Shader RI, Georgotas A, Greenblatt DJ, Harmantz JS, Allen MD. Impaired absorption from clorazepate by magnesium aluminium hydroxide. Clini Pharmacol Ther 1978; 24: 308–15.Google Scholar
  24. 24.
    Veyssier P. Macrolides in geriatric practice. In: Bryskier A, Neu H, Tulkens JP, editors. Macrolides. In press.Google Scholar
  25. 25.
    Spino M. The quinolones. An important group of drugs for the elderly. Can J Physiol Pharmacol 1987; 120: 242–57.Google Scholar
  26. 26.
    Lamy PP. In: Prescribing for the elderly. Littleton (Mass) Wright PSG, 1980.Google Scholar
  27. 27.
    Forbes GB, Reina JC. Adult lean body mass declines with age. Some longitudinal observations. Metabolism 1978; 19: 653–63.Google Scholar
  28. 28.
    Owen JA, Sitar DS, Berger L, Brownell C, Duke PC, Mitenko PA. Age related morphine kinetics. Clin Pharmacol Ther 1983; 34: 364–8.Google Scholar
  29. 29.
    Jung D, Mayersohn M, Perrier D, Calkins J, Saunders R. Thiopental disposition as a function of age in female patients undergoing surgery. Anesthesiology 1982; 56: 263–8.Google Scholar
  30. 30.
    Sack KE. Update on NSAIDs in the elderly. Geriatrics 1989; 44: 71–90.Google Scholar
  31. 31.
    Greenblatt DJ, Allen MD, Locnisker A, Harmatz JS, Schader RI. Lorazepam kinetics in the elderly. Clin Pharmacol Ther 1979; 26: 103–13.Google Scholar
  32. 32.
    Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, Wilkinson GR. Effects of aging and liver disease on lorazepam. Clin Pharmacol Ther 1978; 24: 411–9.Google Scholar
  33. 33.
    Miller AK, Adir J, Vestal RE. Tolbutamide binding to plasma proteins of young and old human subjects. J Pharm Sc 1978; 67: 1192–3.Google Scholar
  34. 34.
    Hayes MJ, Langman MJS, Short AH. Changes in drug metabolism with increasing age II Phenytoin clearance and protein binding. Br J Clin Pharmacol 1975; 2: 73–9.Google Scholar
  35. 35.
    Roberts RK, Wilkinson GR, Branch RA, Schenker S. Effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide (librium) Gastroenterology 1978; 75: 479–85.Google Scholar
  36. 36.
    Vestal RE. Drug use in the elderly. A review of problems and special considerations. Drugs 1978; 16: 358–82.Google Scholar
  37. 37.
    Ludwig E, Csiba A, Magyar T, Szöcs G, Graber H. Age associated pharmacokinetics changes of metronidazole. Int J Clin Pharmacol Ther Toxicol 1983; 21: 87–91.Google Scholar
  38. 38.
    Beermaun B, Hellstroem K, Lindstroem B. Binding site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells. Clin Pharmacol Ther 1975; 17: 424–432.Google Scholar
  39. 39.
    Brandfonbrener M, Landowne M, Shock NW. Changes in cardiac output with age. Circulation 1955; 12: 557–66.Google Scholar
  40. 40.
    Vestal RE, Norris AH, Tobin JD, Cohen BH, Shock NW, Andres R. Antipyrin metabolism in man. Influence of age, alcohol, caffeine and smoking. Clin Pharmacol Ther 1975; 18: 425–32.Google Scholar
  41. 41.
    Swift CG, Homeida M, Halliwell M, Roberts CJC. Antipyrine disposition and liver size in elderly. Eur J Clin Pharmacol 1978; 14: 149.Google Scholar
  42. 42.
    Crooks J, Omalley K, Stevenson IH. Pharmacokinetics in the elderly. Clin Pharmacokinet 1976; 1: 280–96.Google Scholar
  43. 43.
    Dwoll M, Abernathy DR, Ameer B. Acetaminophen kinetics in the elderly. Clin Pharmacol Ther 1982; 31: 151–6.Google Scholar
  44. 44.
    Abernethy DR, Greenblatt DJ, Shader RI. Imipramine and desipramine disposition in the elderly. J Pharmac Ther 1985; 232: 183–7.Google Scholar
  45. 45.
    Larrey D, Tinel M, Pessayre D. Formation of inactive cytochrome p450 Fe (11) metabolites complexes with several erythromycin derivatives but not with josamycin or midecamycin in rats. Biochem Pharmacol 1983; 32: 1487–93.Google Scholar
  46. 46.
    Prince RA, Wing DS, Weinberger MM, Hendeles LS, Riegelman S. Effects of erythromycin on theophyllin kinetics. Allergy Clin Immunol 1981; 68: 427–31.Google Scholar
  47. 47.
    Duvaldestin P, Cantineau JP, Valente E. Pharmacocinétique et pharmacodynamique des medicaments utilisés dans la sédation en réanimation. In: Actualités en réanimation et urgences. Paris: Arnette Ed, 1992: 3–14.Google Scholar
  48. 48.
    Wilkinson GR, Scand DG. A physiological approach to hepatic drug clearance. Clinical Pharmacol and Therap 1975; 18: 377–90.Google Scholar
  49. 49.
    Turner PV, Renton KW. The interaction between carbamazepine and erythromycin. Can J Physiol Pharmacol 1989; 67: 582–6.Google Scholar
  50. 50.
    Billaud Guillemain R, Fortmean N, Kitzis MD, Dreyfus G, et al. Interactions between roxithromycin and cyclosporin in heart transplant patients. Clin Pharmacokinetic 1990; 196: 499–502.Google Scholar
  51. 51.
    Hughes FC. Accidents psychiques liés à l'inhibition du catabolisme des benzodiazepines. Rev Med Interne 1987; 8: 433–6.Google Scholar
  52. 52.
    Farah F, Taylor W, Rawlins MD. Hepatic drug acetylation and oxydation effects of aging in man. Br Med J 1977; 2: 155–6.Google Scholar
  53. 53.
    Gachalyi B, Vas A, Hajos P, Kaldar A. Acetylator phenotypes effect of age. Eur J Clin Pharmacol 1984; 26: 43–8.Google Scholar
  54. 54.
    Chauvin M. Métabolisme des drogues utilisées pour la sédation en réanimation. In: Actualitds en réanimation et urgences. Paris: Amette Ed, 1992: 15–23.Google Scholar
  55. 55.
    Bauer LA, Blouin RA. Age and phenytoin kinetics in adult epileptics. Clin Pharmacol Ther 1982; 31: 301–4.Google Scholar
  56. 56.
    Furlanut M, Benetello P. The pharmacokinetics of tricyclic antidepressant drugs in the elderly. Pharmacol Res 1990; 22: 15–25.Google Scholar
  57. 57.
    Shin SG, Juan D, Ranmohan M. Theophylline pharmacokinetics in normal elderly subjects. Clin Pharmacol Ther 1988; 44: 522–30.Google Scholar
  58. 58.
    Graham G. Pharmacokinetics and metabolism of non steroïdal antiinflammatory drugs. Med J Aust 1987; 147:597–602.Google Scholar
  59. 59.
    Wall RT. Use of analgesics in the elderly. Clin Geriatr Med 1990; 6: 345–64.Google Scholar
  60. 60.
    Abernethy DR. Altered pharmacodynamics of cardiovascular drugs and their relations to altered pharmacokinetics in elderly patients. Clin Geriatr Med 1990; 6(2): 285–92.Google Scholar
  61. 61.
    Wilkinson GR. Drug distribution and renal excretion in the elderly. J Chron Dis 1983; 36: 91–102.Google Scholar
  62. 62.
    Bardin C, Clavier M, Darchis JP, Chauvin M, Veyssier P, Farinotti R. Steady state pharmacokinetics of oral ofloxacin in elderly patients. 17th I.C.C. Berlin, 1991.Google Scholar
  63. 63.
    Veyssier P, Humbert G, Modai J, Fourtillan B. Pharmacokinetics of ofloxacin after single and repeated oral dosage (28 p) comparison with kinetics in young patients (8) and elderly (12). 3rd Intern. Congress on quinolones, Vancouver, 1990.Google Scholar
  64. 64.
    Parent M, Saint Laurent M, Lebel M. Safety of fleroxacin coadministered with theophylline to young and elderly volunteers. Antimicrob Agents Chemother 1990; 34: 1249–53.Google Scholar
  65. 65.
    Taburet AM, Devillers A, Thomare P, Fillastre JP, Veyssier P, Singlas E. Disposition of fleroxacin a new trifluoroquinolone and its metabolites. Pharmaco-kinetics in elderly patients. Clin Pharmacokinet 1990; 19: 80–8.Google Scholar
  66. 66.
    Stroshane RM, Silverman MH, Sauerschell R, Brown RR, Boddy AW, Cook JA. Preliminary study of the pharmacokinetics of oral amifloxacin in elderly subjects. Antimicrob Agents Chemother 1990; 34: 751–4.Google Scholar
  67. 67.
    Machbanks CR, Mikolich DJ, Mayer KH, Zinner SH, Dudley MN. Pharmacokinetics and bioavailability of intravenous to oral enoxacin in elderly patients with complicated urinary tract infections. Antimicrob Agents Chemother 1990; 34: 1966–72.Google Scholar
  68. 68.
    Ljunberg B, Nilsson Ehle I. Advancing age and acute infection influence the kinetics of ceftazidime. Scand J Infect Dis 1989; 21: 327–332.Google Scholar
  69. 69.
    Veyssier P, Devillers A, Domart Y, Fourtillan JB, Bryskier A, Procyk T. Pharmacokinetics of cefodizime in elderly patients with moderate to severe renal impairment. J Antimicrob Chemother 1990; 26 Suppl: 77–81.Google Scholar
  70. 70.
    Ludwig E, Szekely E, Csiba A, Graber H. Pharmacokinetics of cefotaxime and desacetylcefotaxime in elderly patients. Drugs 1988; 35 Suppl 2: 51–6.Google Scholar
  71. 71.
    Barbhaiya RH, Knupp CA, Pittman KA, Tenney J, Martin RR. Effect of age and gender on pharmacokinetics of cefepime. 16th I.C.C., Jerusalem, 1989.Google Scholar
  72. 72.
    Shimada K. Clinical experience with ceftazidime in aged patients. Res Clin For 1988; 10: 57–69.Google Scholar
  73. 73.
    Highbee MN, Swenson E, Gooch III WM. Pharmacokinetics of ceftazidime in elderly patients. Clin Pharm 1989; 8: 59–62.Google Scholar
  74. 74.
    Deeter RG, Weinstein MP, Swanson KA, Gross JS, Bailey LC. Cross over assessment of serum bactericidal activity and pharmacokinetics of five broad spectrum cephalosporins in the elderly. Antimicrob Agents Chemother 1990; 34: 1007–13.Google Scholar
  75. 75.
    Blouin RA, Kneer J, Stoeckel K. Pharmacokinetics of intravenous cefetamet (RO 158074) and oral cefetamet pivoxil (RO 158075) in young and elderly subjects. Antimicrob Agents Chemother 1989; 33: 291–6.Google Scholar
  76. 76.
    Reid JL, MacDonald NJ, Lees KR, Elliott HL. Angiotension converting enzyme inhibitors in the elderly. Am Heart J 1989; 117: 751–755.Google Scholar
  77. 77.
    Flamenbaum W. Diuretic use in the elderly: potential for diuretic induced hypokaliemia. Am J Med 1986; 57: 38A-43A.Google Scholar
  78. 78.
    Abrams SML, Baker LRI, Crome P, White AST, Johnston A, et al. Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment. Postgrad Med J 1988; 64: 361–3.Google Scholar
  79. 79.
    Woodhouse KW, Wynne H. The pharmacokinetics of non steroïdal antiinflammatory drugs in the elderly. Clin Pharmacokinet 1987; 12: 111–22.Google Scholar
  80. 80.
    Advenier C, Roux A, Gobert C, et al. Pharmacokinetics of ketoprofen in the elderly. Br J Clin Pharmacol 1983; 16: 65–70.Google Scholar
  81. 81.
    MoVerry RM, Lethbridge J, Martin N, et al. Pharmacokinetics of naproxen in elderly patients. Eur J Clin Pharmacol 1986; 31: 463–8.Google Scholar
  82. 82.
    Cohen A, Basch C. Steady state pharmacokinetics of naproxen in young and elderly healthy volunteers. Seminars in arthritis and rheumatism; 1988; 17 Suppl 2: 7–11.Google Scholar
  83. 83.
    Woodhouse KW, Wynne H. The pharmacokinetics of non steroidal anti inflammatory drugs in the elderly. Clin Pharmacokin 1987; 12: 111–22.Google Scholar
  84. 84.
    Bannwarth B, Netter P, Manciaux MA, Royer RJ. Pharmacocinetique des antiinflammatoires non stéroï-diens chez le sujet age. Therapie 1988; 43: 447–450.Google Scholar
  85. 85.
    Mignot A, Lefebvre MA, Couet W, Dourthe C, Marechaud R, Fourtillan JB. Pharmacocinetique du sulindac chez des patients ages présentant une pathologie articulaire inflammatoire. Therapie 1989; 44:253–6.Google Scholar
  86. 86.
    Michel P, Grellet J, Saux MC. Determination des corrélations entre les principaux paramètres pharmacocinétiques et les facteurs physiopathologiques de la flécamide chez les sujets âgés. Therapie 1991; 46: 179–82.Google Scholar
  87. 87.
    Stoeckel K, Pfefen JP, Mayersohn M, Schoerlin MP, et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. Acta Psychiatr Scand 1990; Suppl 360: 94–7.Google Scholar
  88. 88.
    Singleton MA, Rosen JI, Fisher DM. Pharmacokinetics of fentanyl in the elderly. Br J Anaesth 1988; 60: 619–22.Google Scholar
  89. 89.
    Baksi A, Edwards JS. Pharmacokinetics in the elderly. J Cardiovasc Pharmacol 1989; 14 Suppl 10: S33–5.Google Scholar
  90. 90.
    Donnelly R, Elliott HL. Factors influencing the response to calcium antagonists in elderly patients with hypertension and ischemic heart disease. Exp Gerontol 1990; 25: 375–81.Google Scholar
  91. 91.
    Fisch HU, Backtir G, Kalarganis G, Minder A, Bircher J. Excessive motor impairment two hours after triazolam in the elderly. Eur J Clin Pharmacol 1990; 38: 229–32.Google Scholar
  92. 92.
    Greenblatt DJ, Allen MD, Shader RI. Toxicity of high dose flurazepam in the elderly. Clin Pharmacol Ther 1971; 29: 424–31.Google Scholar
  93. 93.
    Bender AD. Pharmacologic aspects of aging. A survey of the effect of increasing age on drug activity in adults. J Am Geriatr Soc 1964; 12: 114–34.Google Scholar
  94. 94.
    Phister JE, Jue SG, Cusack J. Problems in the use of anticancer drugs in the elderly. Drugs 1989; 37: 551–65.Google Scholar
  95. 95.
    Health care in the elderly. Report of the technical group on use of medicaments in the elderly — W.H.O. Drugs 1981; 22: 279–94.Google Scholar
  96. 96.
    Burtzyn Goldberg P, Roberts J. Pharmacological basis for developing rational drug regimens for elderly patients. Med Clin North Am 1983; 67(2): 315–31.Google Scholar
  97. 97.
    Cadieux R. Drug interactions in the elderly. How multiple drug use increases risk exponentially. Postgrad Med 1989; 86(8): 179–86.Google Scholar
  98. 98.
    Chiverton SG, Hunt RH. Pharmacokinetics and pharmacodynamics of treatment for peptic ulcer disease in the elderly. Am J Gastroenterol 1988; 83: 211–5.Google Scholar
  99. 99.
    Van der Meer JWM, Kenning JJ, Scheygroud HW. The influence of gastric acid on the bioavailability of ketoconazole. J Antimicrob Chemother 1980; 6: 552–4.Google Scholar
  100. 100.
    Platt D, Bauer M, Eicher H. Pharmacokinetics of ranitidine in geriatric patients with multiple diseases. Arch Gerontol Geriatr 1989; 8: 139–50.Google Scholar
  101. 101.
    Mungall D, Talbert RL, Phillips C. Sucralfate and warfarin. Ann Intern Med 1983; 98: 557 (1).Google Scholar
  102. 102.
    Allgayer H, Rollinghoff W, Baumgartner G. Absence of in vivo and in vitro interactions of magnesium hydroxide containing antacid with cimetidine in peptic ulcer. Gastroenterol 1983; 21: 351–4.Google Scholar
  103. 103.
    Regardh CG. Pharmacokinetics and metabolism of omeprazole. Scand J Gastroenterol 1986; 118 Suppl: 99–104.Google Scholar
  104. 104.
    Grolleau JY. Ergotisme aigu lots d'une association josamycine tartrate d'ergotamine. Therapie 1981; 36: 319–321.Google Scholar
  105. 105.
    Prince RA, Wing DS, Weinberger MM, Hendeles LS, Riegelman S. Effects of erythromycin on theophylline kinetics. Allergy Clin Immunol 1981; 68: 427–31.Google Scholar
  106. 106.
    Bartle WR. Possible warfarin erythromycin interaction. Arch Intern Med 1980; 140: 945–7.Google Scholar
  107. 107.
    Friedman HS, Bonventre MV. Erythromycin induced digoxin toxicity. Chest 1982; 82: 202–5.Google Scholar
  108. 108.
    Turner PV, Renton KW. The interaction between carbamazepine and erythromycin. Can J Physiol Pharmacol 1989; 67: 582–6.Google Scholar
  109. 109.
    Hughes FC. Accidents psychiques lies a l'inhibition du catabolisme des benzodiazepines. Rev Med Interne 1987; 8: 433–6.Google Scholar
  110. 110.
    Sands M, Brown RB. Interaction of cyclosporine with antimicrobial agents. Rev Infect Dis 1989; 11: 691–7.Google Scholar
  111. 111.
    Lowenthal DT. Drug therapy in the elderly. Special considerations. Geriatrics 1987; 42: 77–82.Google Scholar
  112. 112.
    Meyers BM, Wilkinson P. Clinical pharmacokinetics of antibacterial drugs in the elderly. Implications for selection and dosage. Clin Pharmacokinet 1989; 17(6): 385–95.Google Scholar
  113. 113.
    Kruse WHH. Problems and pitfalls in the use of benzodiazepines in the elderly. Drug Saf 1990; 5(5): 328–44.Google Scholar
  114. 114.
    Abernethy DR, Azarnoff D. Pharmacokinetic investigations in elderly patients. Clinical and ethical considerations. Clin Pharmacokinet 1990; 19(2): 89–93.Google Scholar
  115. 115.
    Sack KE. Update on NSAIDs in the elderly. Geriatrics 1989; 44: 71–90.Google Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • Pierre Veyssier
    • 1
  1. 1.Centre Hospitalier de CompiegneFrance

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