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Drug Dosage in the Elderly

Is it Rational?

Abstract

Pharmacotherapy in the elderly requires an understanding of the age-dependent changes in function and composition of the body. Aging is characterised by a progressive loss of functional capacities of most if not all organs, a reduction in response to receptor stimulation and homeostatic mechanisms, and a loss of water content and an increase of fat content in the body.

The most important pharmacokinetic change in old age is a decrease in the excretory capacity of the kidney; in this regard, the elderly should be considered as renally insufficient patients. The decline in the rate of drug metabolism with advancing age is less marked. In addition, the volume of distribution and the oral bioavailability of drugs may be changed in the elderly compared with younger individuals.

Average dosage adjustments for the aged can be derived from simple equations and mean pharmacokinetic parameters from older and younger adults. However, these average dose adjustment factors neglect the large variation in the decline in organ functions among the elderly. Individual dose adjustment factors can be obtained from the drug clearance in a particular patient, where clearance/fractional bioavailability (CL/f) may be calculated from the area under the plasma concentration-time curve (AUC) of the drug in question.

Using pharmacokinetic guidelines for dose adjustments, the same plasma drug concentrations result in elderly as in younger adults. However, we are frequently confronted with pharmacodynamic changes in old age which alter the sensitivity to drugs, irrespective of changes in drug disposition. For instance, the sensitivity of the cardiovascular system to β-adrenergic agonists and antagonists decreases in old age and the incidence of orthostatic episodes in response to drugs that lower blood pressure is increased. The CNS is especially vulnerable in the elderly; agents that affect brain function (anaesthetics, opioids, anticonvulsants, psycho-tropic drugs) must be used very cautiously in this age group.

The increased responsiveness to drugs in the elderly renders the measurement of drug plasma concentrations an attractive method to monitor pharmacotherapy in this age group. Sensitive technology to quantitatively determine plasma drug concentrations is available. However, optimal therapeutic plasma concentrations have not been established for most drugs in the elderly. Investigations concerning drug pharmacokinetic-pharmacodynamic relationships in the aged are an important area of future work in clinical pharmacology.

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References

  1. Nolan L, O’Malley K. Prescribing in the elderly: I. sensitivity of the elderly to adverse drug reactions. J Am Geriatr Soc 1988; 36: 142–9

    PubMed  CAS  Google Scholar 

  2. Vestal RE, Cusack BJ. Pharmacology and aging. In: Schneider EL, Rowe JW, editors. Handbook of the biology of aging. 3rd ed. San Diego: Academic Press, 1990: 349–83

    Google Scholar 

  3. Tumer N, Scarpace PJ, Lowenthal DT. Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 1992; 32: 271–302

    PubMed  CAS  Google Scholar 

  4. Gosney M, Tillis R. Prescription of contraindicated and interacting drugs in elderly patients admitted to hospital. Lancet 1984; II: 564–7

    Google Scholar 

  5. Adams KHR, Al-Hamouz S, Edmund E. Inappropriate prescribing in the elderly. J R Coll Physicians Lond 1987; 21: 39–41

    PubMed  CAS  Google Scholar 

  6. Divoll MK, Greenblatt DY. Drug interactions and adverse drug reactions in the elderly. In: Swift LG, editor. Clinical pharmacology in the elderly. New York: Marcel Decker, 1987: 119–45

    Google Scholar 

  7. Grymonpre RE, Mitenko PA, Sitar DS, et al. Drug associated hospital admittances in older medical patients. J Am Geriatr Soc 1988; 36: 1092–8

    PubMed  CAS  Google Scholar 

  8. Beard K. Adverse reactions as a cause of hospital admission in the aged. Drugs Aging 1992; 2: 356–67

    PubMed  CAS  Google Scholar 

  9. Klein-Schwartz W, Oderda GM. Poisoning in the elderly: epidemiological, clinical and management considerations. Drugs Aging 1991; 1: 67–89

    PubMed  CAS  Google Scholar 

  10. Do doctors short-change old people [editorial]? Lancet 1993; 342: 1–2

    Google Scholar 

  11. Wetle T. Age as a risk factor for inadequate treatment. JAMA 1987; 258: 516

    PubMed  CAS  Google Scholar 

  12. Forman DE, Rich MW. Management of acute myocardial infarction in the elderly. Drugs Aging 1996; 8: 358–77

    PubMed  CAS  Google Scholar 

  13. Gurwitz JH, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991; 114: 956–66

    PubMed  CAS  Google Scholar 

  14. Shaw AB. Age as a basis for health care rationing: support for agist policies. Drugs Aging 1996; 9: 403–5

    PubMed  CAS  Google Scholar 

  15. Birnbaum LS. Pharmacokinetic basis of age-related changes in sensitivity to toxicants. Annu Rev Pharmacol 1991; 31: 101–28

    CAS  Google Scholar 

  16. World Health Organization: health care in the elderly. Drugs 1981; 22: 279–94

  17. Franke H. Wesen und Bedeutung der Polypathie und Multimorbidität in der Altersheilkunde. In: Platt D, editor. Handbuch der Gerontologie. Vol. 1. Stuttgart: Gustav Fischer, 1983: 449–70

    Google Scholar 

  18. Hauptverband der Sozialversicherungsträger in Österreich. Medikamentenerfassung. ÖSTAT 1994

  19. Baum C, Kennedy DL, Forbes MB, et al. Drug use in the United States in 1981. JAMA 1981; 251: 1293–7

    Google Scholar 

  20. Christopher LJ. Drug prescribing and compliance in the elderly. In: Swift CG, editor. Clinical pharmacology in the elderly. New York: Marcel Decker, 1987: 103–17

    Google Scholar 

  21. Tregaskis BF, Stevenson IH. Pharmacokinetics in old age. Br Med Bull 1990; 46: 9–21

    PubMed  CAS  Google Scholar 

  22. Ruiz JG, Array S, Lowenthal DT. Therapeutic drug monitoring in the elderly. Am J Ther 1996; 3: 839–60

    PubMed  Google Scholar 

  23. Morrow D, Leirer V, Sheik J. Adherence and medication instructions: review and recommendations. J Am Geriatr Soc 1988; 36: 1147–60

    PubMed  CAS  Google Scholar 

  24. Cramer JA. Enhancing patient compliance in the elderly: role of packaging aids and monitoring. Drugs Aging 1998; 12: 7–15

    PubMed  CAS  Google Scholar 

  25. Dice JF. Cellular and molecular mechanisms of aging. Physiol Rev 1993; 73: 149–59

    PubMed  CAS  Google Scholar 

  26. Knight JA. The process and theories of aging. Ann Clin Lab Sci 1995; 25: 1–12

    PubMed  CAS  Google Scholar 

  27. Masoro EJ. Aging: current concepts. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 3–21

    Google Scholar 

  28. Kipling D, Faragher RGA. Progeroid syndromes: probing the molecular basis of aging. J Clin Pathol Mol Pathol 1997; 50: 234–41

    CAS  Google Scholar 

  29. Dyer CAE, Sinclair AJ. The premature aging syndromes: insights into the aging process. Age Aging 1998; 27: 73–80

    CAS  Google Scholar 

  30. Yamabe Y, Sugimoto M, Satoh M, et al. Down-regulation of the defective transcripts of the Werner’s syndrome gene in the cells of patients. Biochem Biophys Res Commun 1997; 236: 151–4

    PubMed  CAS  Google Scholar 

  31. Wu JG, He J, Mountz JD. Effect of age and apoptosis of the mouse homologue of the huWRN gene. Mech Ageing Dev 1998; 103: 27–44

    PubMed  CAS  Google Scholar 

  32. Gafni A. Structural modifications of proteins during aging. J Am Geriatr Soc 1997; 45: 871–80

    PubMed  CAS  Google Scholar 

  33. Miller RA. When will the biology of aging become useful? Future landmarks in biomedical gerontology. J Am Geriatr Soc 1997; 45: 1258–67

    PubMed  CAS  Google Scholar 

  34. Yu BP. Putative interventions. In: Masoro EJ, editor. Handbook of physiology, sect. II: aging. New York: Oxford University Press, 1995: 613–31

    Google Scholar 

  35. Lamy PP. Physiological changes due to age; pharmacodynamic changes of drug action and implications for therapy. Drugs Aging 1991; 1: 385–404

    PubMed  CAS  Google Scholar 

  36. Kohn RR, Monnier VM. Normal aging and its parameters. In: Swift CG, editor. Clinical pharmacology in the elderly. New York: Marcel Dekker, 1987: 3–30

    Google Scholar 

  37. Crockford PM, Harbeck RJ, Williams RM. Influence of age on intravenous glucose tolerance and serum immunoreactive insulin. Lancet 1966; I: 465–7

    Google Scholar 

  38. Lund-Johansen P. The hemodynamics of the aging cardiovascular system. J Cardiovasc Pharmacol 1988; 12Suppl. 8: S20–32

    PubMed  Google Scholar 

  39. Cody RJ. Physiological changes due to age: implications for drug therapy of congestive heart failure. Drugs Aging 1993; 3: 322–34

    Google Scholar 

  40. Lakatta EG. Cardiovascular system. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 413–74

    Google Scholar 

  41. O’Malley K, Kelly JG, Swift CG. Responsiveness to drugs. In: Swift CG, editor. Clinical pharmacology in the elderly. New York: Marcel Dekker, 1987: 83–101

    Google Scholar 

  42. Docherty JR. Aging and the cardiovascular system. J Auton Pharmacol 1986; 6: 77–84

    PubMed  CAS  Google Scholar 

  43. Docherty JR. Cardiovascular responses in ageing. Pharmacol Rev 1990; 42: 103–25

    PubMed  CAS  Google Scholar 

  44. Folkow B, Svanborg A. Physiology of cardiovascular aging. Physiol Rev 1993; 73: 725–64

    PubMed  CAS  Google Scholar 

  45. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 1993; 73: 413–67

    PubMed  CAS  Google Scholar 

  46. Sparrow D, Weiss ST. Respiratory system. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 475–83

    Google Scholar 

  47. Mayersohn MB. Special pharmacokinetic considerations in the elderly. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. 3rd ed. Vancouver (WA): Applied Therapeutics Inc., 1992: 9.1–9.43

    Google Scholar 

  48. Phillips PA, Rolls BJ, Ledingham JG, et al. Reduced thirst after water deprivation in healthy elderly men. N Engl J Med 1984; 311: 753–9

    PubMed  CAS  Google Scholar 

  49. Stachenfeld NS, DiPietro L, Nadel ER, et al. Mechanism of attenuated thirst in aging: role of central volume receptors. Am J Physiol 1997; 272: R148–57

    PubMed  CAS  Google Scholar 

  50. Rowe JW, Andres R, Tobin JD, et al. The effect of age on creatinine clearance in man: a cross-sectional and longitudinal study. J Gerontol 1976; 31: 155–63

    PubMed  CAS  Google Scholar 

  51. Lindeman RD, Tobin J, Shock NW. Longitidinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33: 278–85

    PubMed  CAS  Google Scholar 

  52. Lindeman RD. Renal and urinary tract. In: Masoro EJ, editor. Handbook of physiology. Sect 11: aging. New York: Oxford University Press, 1995: 485–503

    Google Scholar 

  53. Kampmann J, Siersbaeck-Nielsen K, Kristensen M, et al. Rapid evaluation of creatinine clearance. Acta Med Scand 1974; 196: 517–20

    PubMed  CAS  Google Scholar 

  54. Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest 1950; 29: 496–507

    PubMed  CAS  Google Scholar 

  55. Bricker NS, Morrin PAF, Kime SW. The pathological physiology of chronic Bright’s disease: an exposition of the intact nephron hypothesis. Am J Med 1960; 28: 77–98

    PubMed  CAS  Google Scholar 

  56. Klingler C, Preisser L, Barrault MB, et al. Vasopressin V2 receptor mRNA expression and cAMP accumulation in aging rat kidney. Am J Physiol 1997; 272: R1775–82

    PubMed  CAS  Google Scholar 

  57. Wynne HA, Cope LH, Mutch E, et al. The effect of age upon liver volume and apparent blood flow in healthy men. Hepatology 1989; 9: 297–301

    PubMed  CAS  Google Scholar 

  58. Schmucker DL. Aging and drug disposition: an update. Pharmacol Rev 1985; 37: 133–48

    PubMed  CAS  Google Scholar 

  59. Schmucker DL, Woodhouse KW, Wang RK, et al. Effects of age and gender on in vitro properties of human liver microsomal mono-oxygenases. Clin Pharmacol Ther 1990; 48: 365–74

    PubMed  CAS  Google Scholar 

  60. O’Mahony MS, Woodhouse KW. Age, environmental factors and drug metabolism. Pharmacol Ther 1994; 61: 279–87

    PubMed  Google Scholar 

  61. Sotamieni EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 2267 subjects with equal histopathological conditions. Clin Pharmacol Ther 1997; 61: 331–9

    Google Scholar 

  62. Georg J, Byth K, Farrell GC. Age but not gender selectivity affects expression of individual cytochrome P450 proteins in human liver. Biochem Pharmacol 1995; 50: 727–30

    Google Scholar 

  63. Hunt CM, Strater S, Stave GM. Effect of normal aging on the activity of human hepatic cytochrome P450IIE1. Biochem Pharmacol 1991; 40: 1666–9

    Google Scholar 

  64. Hunt CM, Westerkam WR, Stave FM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 1992; 44: 275–83

    PubMed  CAS  Google Scholar 

  65. Transon C, Lecoeur S, Leemann T, et al. Interindividual variability in catalytic activity and immunoreactivity of three major human liver cytochrome P450 isoenzymes. Eur J Clin Pharmacol 1996; 51: 79–85

    PubMed  CAS  Google Scholar 

  66. Roth GS. Hormone receptor changes during adulthood and senescence: significance for aging research. Fed Proc 1979; 38: 1910–4

    PubMed  CAS  Google Scholar 

  67. Nelson JF. The potential role of selected endocrine systems in aging process. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 377–94

    Google Scholar 

  68. Callens A, Vaillant L, Lecomte P, et al. Does hormonal skin aging exist: a study of the influence of different hormone therapy regimens on the skin of postmenopausal women using noninvasive measurement techniques. Dermatology 1996; 193: 289–94

    PubMed  CAS  Google Scholar 

  69. Davidson MB. The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnostics of diabetes mellitus in the elderly. Metabolism 1979; 28: 688–705

    PubMed  CAS  Google Scholar 

  70. Autry CP, Kifor O, Brown EM, et al. Ca2+ receptor mRNA and protein increase in the rat parathyroid gland with increasing age. J Endocrinol 1997; 153: 437–44

    PubMed  CAS  Google Scholar 

  71. Stuck AE, Frey BM, Frey FJ. Kinetics of prednisolone and endogenous cortisol suppression in the elderly. Clin Pharmacol Ther 1988; 43: 354–62

    PubMed  CAS  Google Scholar 

  72. Wilkinson CN, Peskind ER, Raskind MA. Decreased hypothalamic pituitary adrenal axis sensitivity to cortisol feedback inhibition in human aging. Neuroendocrinology 1997; 65: 79–90

    PubMed  CAS  Google Scholar 

  73. Yu S, Abel L, Globerson A. Thymocyte progenitors and T cell development in aging. Mech Ageing Dev 1997; 94: 103–11

    PubMed  CAS  Google Scholar 

  74. Gorgas G, Butch ER, Guan KL, et al. Diminished activation of the MAP kinase pathway in CD3 stimulated T lymphocytes from old mice. Mech Ageing Dev 1997; 94: 71–83

    PubMed  CAS  Google Scholar 

  75. Biasi D, Carletto A, Dellagnola C, et al. Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 1996; 20: 673–81

    PubMed  CAS  Google Scholar 

  76. Rothstein G. Hematopoiesis in the aged: a model of hematopoietic dysregulation? Blood 1993; 82: 2601–4

    PubMed  CAS  Google Scholar 

  77. Chatta GS, Dale DC. Aging and haematopoiesis: implications for treatment with thrombopoietic growth factors. Drugs Aging 1996; 9: 37–47

    PubMed  CAS  Google Scholar 

  78. Zajac BA, West DY, McAleer WJ, et al. Overview of clinical studies with hepatitis B vaccine made by recombinant DNA. J Infect 1986; 13Suppl. A: 35–45

    Google Scholar 

  79. Muravchik S. Immediate and long term nervous system effects of anesthesia in elderly patients. Clin Anesth 1988; 4: 1035–45

    Google Scholar 

  80. Muravchik S. Anesthesia for the elderly. In: Miller R, editor. Anaesthesia. Edinburgh: Churchill Livingstone, 1994: 2143–56

    Google Scholar 

  81. Finch CE. Neuron atrophy during aging: programmed or sporadic. Trends Neurosci 1993; 16: 104–10

    PubMed  CAS  Google Scholar 

  82. Raz N, Gunning FM, Head D, et al. Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. Cereb Cortex 1997; 7: 268–82

    PubMed  CAS  Google Scholar 

  83. Katzman R. Human nervous system. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 325–44

    Google Scholar 

  84. Swift CG. Pharmacodynamics: changes in homeostatic mechanisms, receptor and target sensitivity in the elderly. Br Med Bull 1990; 46: 36–52

    PubMed  CAS  Google Scholar 

  85. Catterson ML, Preskorn SH, Martin RL. Pharmacodynamic and pharmacokinetic considerations in geriatric psychopharmacology. Psychiatr Clin North Am 1997; 20: 205–18

    PubMed  CAS  Google Scholar 

  86. Lefkowitz RJ, Caron MG, Stiles GL. Mechanisms of membrane-receptor regulation: biochemical, physiological, and clinical insights derived from studies of the adrenergic receptors. N Engl J Med 1984; 310: 1570–9

    PubMed  CAS  Google Scholar 

  87. Vestal R, Wood A, Shand D. Reduced β-adrenoreceptor sensitivity in the elderly. Clin Pharmacol Ther 1979; 26: 181–6

    PubMed  CAS  Google Scholar 

  88. White M, Roden R, Minobe W, et al. Age-related changes in β-adrenergic neuroeffector systems in human heart. Circulation 1994; 90: 1225–38

    PubMed  CAS  Google Scholar 

  89. Hardouin S, Mansier P, Bertin B, et al. Beta adrenergic and muscarinic receptor expression are regulated in opposite ways during senescence in rat left ventricle. J Mole Cell Cardiol 1997; 29: 309–29

    CAS  Google Scholar 

  90. Gao EH, Snyder DL, Johnson MD, et al. The effect of age on adenosine A1 receptor function in the rat heart. J Mole Cell Cardiol 1997; 29: 593–602

    CAS  Google Scholar 

  91. Ibarra M, Terron JA, Lopez Guerrero JJ, et al. Evidence for an age dependent functional expression of α1D adrenoceptors in the rat vasculature. Eur J Pharmacol 1997; 322: 221–4

    PubMed  CAS  Google Scholar 

  92. Poller U, Nedelka G, Radke J, et al. Age dependent changes in cardiac muscarinic receptor function in healthy volunteers. J Am Coll Cardiol 1997; 29: 187–93

    PubMed  CAS  Google Scholar 

  93. Wong DF, Young D, Wilson PD, et al. Quantification of neuroreceptors in the living human brain. D2-like dopamine receptors: theory, validation, and changes during normal aging. J Cereb Blood Flow Metab 1997; 17: 316–30

    PubMed  CAS  Google Scholar 

  94. Tanner C. Epidemiology of Parkinson’s disease. Neurol Clin 1992; 10: 317–28

    PubMed  CAS  Google Scholar 

  95. Lanius RA, Pasqualotto BA, Shaw CA. Age-dependent expression, phosphorylation and function of neurotransmitter receptors: pharmacological implications. Trends Pharmacol Sci 1993; 14: 403–8

    PubMed  CAS  Google Scholar 

  96. Gutierrez A, Khan ZU, Miralles CP, et al. GABAA receptor subunit expression changes in the rat cerebellum and cerebral cortex during aging. Mol Brain Res 1997; 45: 59–70

    PubMed  CAS  Google Scholar 

  97. Ou XR, Walsh JR. Aging decreases rebound synaptic excitation produced by removal of NMDA receptor block in the striatum. Exp Brain Res 1997; 114: 590–4

    PubMed  CAS  Google Scholar 

  98. Renganathan M, Messi ML, Delbono O. Dihydropyridine receptor — ryanodine receptor uncoupling in aged skeletal muscle. J Membr Biol 1997; 157: 247–53

    PubMed  CAS  Google Scholar 

  99. Obeid LM, Venable ME. Signal transduction in cellular senescence. J Am Geriatr Soc 1997; 45: 361–6

    PubMed  CAS  Google Scholar 

  100. Swift CG, Triggs EJ. Clinical pharmacokinetics in the elderly. In: Swift CG, editor. Clinical pharmacology in the elderly. New York: Marcel Dekker Inc., 1987: 31–82

    Google Scholar 

  101. Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med 1989; 321: 303–9

    PubMed  CAS  Google Scholar 

  102. Andreasen F, Hansen N, Husted SE, et al. The influence of age on renal and extrarenal effects of furosemide. Br J Clin Pharmacol 1984; 18: 65–74

    PubMed  CAS  Google Scholar 

  103. Hymans DE. The elderly patient: a special case for diuretic therapy. Drugs 1986; 31Suppl. 4: 138–53

    Google Scholar 

  104. Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly. Clin Pharmacol Ther 1995; 57: 42–51

    PubMed  CAS  Google Scholar 

  105. Kato R, Vassanelli P, Frontino G, et al. Variation in the activity of liver microsomal drug-metabolizing enzymes in rats in relation to age. Biochem Pharmacol 1964; 13: 1037–51

    PubMed  CAS  Google Scholar 

  106. Durnas C, Loi CH, Cusack BY. Hepatic drug metabolism and aging. Clin Pharmacokinet 1990; 19: 359–89

    PubMed  CAS  Google Scholar 

  107. Van Bezooijen CF. Influence of age-related changes in rodent liver morphology and physiology on drug metabolism — a review. Mech Ageing Dev 1984; 25: 1–72

    PubMed  Google Scholar 

  108. Greenblatt DJ, Divoll M, Abernethy DR, et al. Antipyrine kinetics in the elderly: prediction of age-related changes in benzodiazepine oxidizing capacity. J Pharmacol Exp Ther 1982; 220: 120–6

    PubMed  CAS  Google Scholar 

  109. Vestal RE, Norris AH, Tobin JD, et al. Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking. Clin Pharmacol Ther 1975; 18: 425–32

    PubMed  CAS  Google Scholar 

  110. Castleden CM, Swift CG. Hypnotics, sedatives, and anticonvulsants. In: Swift CG, editor. Clinical pharmacology in the elderly. New York: Marcel Dekker Inc., 1987: 281–341

    Google Scholar 

  111. Annesley T. Special considerations for geriatric therapeutic drug monitoring. Clin Chem 1989; 35: 1337–41

    PubMed  CAS  Google Scholar 

  112. Robertson DRC, Wood ND, Everest H, et al. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. Br J Clin Pharmacol 1989; 28: 61–9

    PubMed  CAS  Google Scholar 

  113. Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics of indomethacin in the elderly. Clin Pharmacokinet 1993; 24: 428–34

    PubMed  CAS  Google Scholar 

  114. Bernus I, Dickinson RG, Hooper WD, et al. Anticonvulsant therapy in aged patients: clinical pharmacokinetic considerations. Drugs Aging 1997; 10: 278–89

    PubMed  CAS  Google Scholar 

  115. Greenblatt DY, Shader RI, Harmatz JS. Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacol 1989; 29: 866–72

    PubMed  CAS  Google Scholar 

  116. Advenier C, Saint-Aubin A, Gobert C, et al. Pharmacokinetics of isoniazid in the elderly. Br J Clin Pharmacol 1980; 10: 167–8

    PubMed  CAS  Google Scholar 

  117. Gachalyi B, Vas A, Hajos P, et al. Acetylator phenotypes: effect of age. Eur J Clin Pharmacol 1984; 26: 43–5

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  119. Abernethy DR, Schwartz JB, Todd EL, et al. Verapamil pharmacodynamics and disposition in young and elderly hypertensive patients. Ann Intern Med 1986; 105: 329–36

    PubMed  CAS  Google Scholar 

  120. Robertson DRC, Waller DG, Renwick AG, et al. Age-related changes in the pharmacokinetics and pharmacodynamics of nifedipine. Br J Clin Pharmacol 1988; 25: 297–305

    PubMed  CAS  Google Scholar 

  121. Rosenkranz B, Winkelmann BR, Parnham MJ. Clinical pharmacokinetics of molsidomine. Clin Pharmacokinet 1996; 30: 372–84

    PubMed  CAS  Google Scholar 

  122. Kelly JG, McGarry K, O’Malley K, et al. Bioavailability of labetalol increases with age. Br J Clin Pharmacol 1982; 14: 304–5

    PubMed  CAS  Google Scholar 

  123. Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol 1983; 5: 1093–6

    PubMed  CAS  Google Scholar 

  124. Barbhaiya RH, Shokla UA, Green DS. Single-dose pharmacokinetics of nefazodone in healthy young and elderly subjects and in subjects with renal or hepatic impairment. Eur J Clin Pharmacol 1995; 49: 221–8

    PubMed  CAS  Google Scholar 

  125. Evans MA, Triggs EJ, Broe GA, et al. Systemic availability of orally administered L-dopa in the elderly parkinsonian patient. Eur J Clin Pharmacol 1980; 17: 215–21

    PubMed  CAS  Google Scholar 

  126. Feely J. Factors affecting the response to inhibition of drug metabolism by cimetidine — dose response and sensitivity of elderly and induced subjects. Br J Clin Pharmacol 1984; 17: 77–81

    PubMed  CAS  Google Scholar 

  127. Vestal RE, Cusack BJ, Mercer GD, et al. Age and drug interactions: I. effect of cimetidine and smoking on the oxidation of theophylline and Cortisol in healthy men. J Pharmacol Exp Ther 1987; 241: 488–500

    PubMed  CAS  Google Scholar 

  128. Divoll M, Greenblatt DJ, Abernethy DR, et al. Cimetidine impairs clearance of antipyrine and desmethyldiazepam in the elderly. J Am Geriatr Soc 1982; 30: 684–9

    PubMed  CAS  Google Scholar 

  129. Chandler HH, Blouin RA. Dietary influence on drug disposition. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. 3rd ed. Vancouver (WA): Applied Therapeutics Inc., 1992: 12.1–12.17

    Google Scholar 

  130. Williams FM, Wynne H, Woodhouse KW, et al. Plasma aspirin esterase: the influence of old age and frailty. Age Ageing 1989; 18: 39–42

    PubMed  CAS  Google Scholar 

  131. Wynne, HA, Cope LH, Herd B, et al. The association of age and frailty with paracetamol conjugation in man. Age Ageing 1990; 19: 419–24

    PubMed  CAS  Google Scholar 

  132. Vestal RE, Montamat SC, Nielson CP. Drugs in special age groups: the elderly. In: Melmon KL, Morrelli HF, Hoffman BB, et al. Clinical pharmacology, basic principles in therapeutics. New York: McGraw-Hill, 1992: 851–74

    Google Scholar 

  133. Wallace SM, Verbeek RK. Plasma protein binding of drugs in the elderly. Clin Pharmacokinet 1987; 12: 41–72

    PubMed  CAS  Google Scholar 

  134. Bendayan R, Pieper JA, Stewwart RB, et al. Influence of age on serum protein binding of propranolol. Eur J Clin Pharmacol 1984; 26: 251–4

    PubMed  CAS  Google Scholar 

  135. Davies D, Grossman SH, Kitchell BB, et al. Age related changes in plasma protein binding of lignocaine and diazepam. Br J Clin Pharmacol 1985; 19: 261–5

    Google Scholar 

  136. Abernethy DR, Kerzner L. Age effects on Alpha-1-acid glycoprotein concentration and imipramine plasma protein binding. J Am Geriatr Soc 1984; 32: 705–8

    PubMed  CAS  Google Scholar 

  137. Campion EW, Avorn J, Reder VA, et al. Overmedication of low-weight elderly. Arch Intern Med 1987; 147: 945–7

    PubMed  CAS  Google Scholar 

  138. Baime MJ, Nelson JB, Castel DO. Aging of the gastrointestinal system. In: Hazzard WR, Bierman EL, Blass JP, editors. Principles of geriatric medicine and gerontology. 3rd ed. New York: McGraw-Hill, 1994: 665–81

    Google Scholar 

  139. Holt PR. The gastrointestinal tract. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 505–54

    Google Scholar 

  140. Majumdar APN, Fligiel SEG, Jaszewski R. Gastric mucosal injury and repair: effect of aging. Histol Histopathol 1997; 12: 491–501

    PubMed  CAS  Google Scholar 

  141. Johnson SL, Mayersohn M, Conrad KA. Xylose disposition in humans as a function of age. Clin Pharmacol Ther 1986; 39: 697–702

    PubMed  CAS  Google Scholar 

  142. Yoshikawa TT, Norman DC. Treatment of infections in elderly patients. Med Clin North Am 1995; 79: 651–61

    PubMed  CAS  Google Scholar 

  143. Rubin PC, Scott PYW, Reid JL. Prazosin disposition in young and elderly subjects. Br J Clin Pharmacol 1981; 12: 401–4

    PubMed  CAS  Google Scholar 

  144. Cusack B, Kelly JG, O’Malley K. The cardiac glycosides. In: Swift CG, editor. Clinical pharmacology in the elderly. New York: Marcel Dekker, Inc., 1987: 149–77

    Google Scholar 

  145. Goa KL, Sorkin EM. Gabapentin: a review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993; 46: 409–27

    PubMed  CAS  Google Scholar 

  146. Roskos KV, Maibach HI. Percutaneous absorption and age. Drugs Aging 1992; 2: 432–49

    PubMed  CAS  Google Scholar 

  147. Roskos KV, Maibach HI, Guy RA. The effect of aging on percutaneous absorption in man. J Pharmacokinet Biopharm 1989; 17: 617–30

    PubMed  CAS  Google Scholar 

  148. Turnheim K. Pitfalls in pharmacokinetic dosage guidelines in renal insufficiency. Eur J Clin Pharmacol 1991; 40: 87–93

    PubMed  CAS  Google Scholar 

  149. Divoll M, Abernethy MA, Ameer B, et al. Acetaminophen kinetics in the elderly. Clin Pharmacol Ther 1982; 31: 151–6

    PubMed  CAS  Google Scholar 

  150. Lemmens HJM, Burm AGL, Hennis PJ, et al. Influence of age on the pharmacokinetics of alfentanil: gender dependence. Clin Pharmacokinet 1990; 19: 416–22

    PubMed  CAS  Google Scholar 

  151. Bertz RJ, Kroboth PD, Kroboth FJ, et al. Alprazolam in young and elderly men: sensitivity and tolerance to psychomotor, sedative and memory effects. J Pharmacol Exp Ther 1997; 281: 1317–29

    PubMed  CAS  Google Scholar 

  152. Vanhaevenbeek M, Siska G, Herchuelz A. Pharmacokinetics of once-daily amikacin in elderly patients. J Antimicrob Chemother 1993; 31: 185–7

    Google Scholar 

  153. Vadiei K, Troy S, Korthbradley J, et al. Population pharmacokinetics of intravenous amiodarone and comparison with two stage pharmacokinetic analysis. J Clin Pharmacol 1997; 37: 610–7

    PubMed  CAS  Google Scholar 

  154. Schulz P, Turner-Tamiyasu K, Smith G, et al. Amitriptyline disposition in young and elderly normal men. Clin Pharmacol Ther 1983; 33: 360–6

    PubMed  CAS  Google Scholar 

  155. Abernethy DR, Gutkowska J, Winterbottom LM. Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: pharmacodynamics in relation to disposition. Clin Pharmacol Ther 1990; 48: 76–86

    PubMed  CAS  Google Scholar 

  156. Ornstein E, Lien CA, Matteu RS, et al. Pharmacodynamics and pharmacokinetics of cis-atracurium in geriatric surgical patients. Anesthesiology 1996; 84: 520–5

    PubMed  CAS  Google Scholar 

  157. Barbhaiya RH, Knupp CA, Pittman KA. Effects of age and gender on pharmacokinetics of cefepime. Antimicrob Agents Chemother 1992; 36: 1181–5

    PubMed  CAS  Google Scholar 

  158. Blouin RA, Stoeckel K. Cefetamet pivoxil clinical pharmacokinetics. Clin Pharmacokinet 1993; 25: 172–88

    PubMed  CAS  Google Scholar 

  159. Greenblatt DJ, Divoll MK, Abernethy DR, et al. Age and gender effects of chlordiazepoxide kinetics: relation to antipyrine disposition. Pharmacology 1989; 38: 327–34

    PubMed  CAS  Google Scholar 

  160. Nilsson-Ehle I, Ljunberg B. Quinolone disposition in the elderly: practical implications. Drugs Aging 1991; 1: 279–88

    PubMed  CAS  Google Scholar 

  161. Herman RJ, Wilkinson GR. Disposition of diazepam in young and elderly subjects after acute and chronic dosing. Br J Clin Pharmacol 1996; 42: 147–55

    PubMed  CAS  Google Scholar 

  162. Divoll M, Greenblatt DJ, Ochs HR, et al. Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex. Anesth Analg 1983; 62: 1–8

    PubMed  CAS  Google Scholar 

  163. Simons KJ, Watson TA, Martin TJ, et al. Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults and children. J Clin Pharmacol 1990; 30: 665–71

    PubMed  CAS  Google Scholar 

  164. Dresner DL, Basta SJ, Ali HH, et al. Pharmacokinetics and pharmacodynamics of doxacurium in young and elderly patients during isoflurane anesthesia. Anesth Analg 1990; 71: 498–502

    PubMed  CAS  Google Scholar 

  165. Silverberg PA, Matteo RS, Ornstein E, et al. Pharmacokinetics and pharmacodynamics of edrophonium in the elderly [abstract]. Anesth Analg 1986; 65 Suppl.: S142

    Google Scholar 

  166. Pflüger KH, Hahn M, Holz JB, et al. Pharmacokinetics of etoposide: correlation of pharmacokinetic parameters with clinical conditions. Cancer Chemother Pharmacol 1993; 31: 350–6

    PubMed  Google Scholar 

  167. Echizen H, Ishizaki T. Clinical pharmacokinetics of famotidine. Clin Pharmacokinet 1991; 21: 178–94

    PubMed  CAS  Google Scholar 

  168. Blychert E, Edgar B, Elmfeldt D, et al. A population study of the pharmacokinetics of felodipine. Br J Clin Pharmacol 1991; 31: 15–24

    PubMed  CAS  Google Scholar 

  169. Singleton MA, Rosen JI, Fisher DM. Pharmacokinetics of fentanyl in the elderly. Br J Anaesth 1988; 60: 619–22

    PubMed  CAS  Google Scholar 

  170. Roncari G, Timm U, Zell M, et al. Flumazenil kinetics in the elderly. Eur J Clin Pharmacol 1993; 45: 585–7

    PubMed  CAS  Google Scholar 

  171. Andreasen F, Hansen N, Husted SE, et al. The pharmacokinetics of furosemide are influenced by age. Br J Clin Pharmacol 1983; 16: 391–7

    PubMed  CAS  Google Scholar 

  172. El-Sayed YM, Islam SI. Effect of age and renal function on gentamicin pharmacokinetic parameters. Int J Clin Pharmacol 1989; 27: 503–9

    CAS  Google Scholar 

  173. Leoni F, Ciolli S, Giuliani G, et al. Attenuated-dose idarubicin in acute myeloid leukaemia of the elderly: pharmacokinetic study and clinical results. Br J Haematol 1995; 90: 169–74

    PubMed  CAS  Google Scholar 

  174. Abernethy DR, Greenblatt DJ, Shader RI. Imipramine and desipramine disposition in the elderly. J Pharmacol Exp Ther 1985; 232: 183–8

    PubMed  CAS  Google Scholar 

  175. Greenblatt DJ, Divoll Allen M, Locniskar A, et al. Lorazepam kinetics in the elderly. Clin Pharmacol Ther 1979; 26: 103–13

    PubMed  CAS  Google Scholar 

  176. Tornatore KM, Logue G, Venuto RC, et al. Pharmacokinetics of methylprednisolone in young and elderly males. J Am Geriatr Soc 1994; 42: 1118–22

    PubMed  CAS  Google Scholar 

  177. Matteo RS, Backus WW, McDaniel DD, et al. Pharmacokinetics and pharmacodynamics of d-tubocurarine and metocurine in the elderly. Anesth Analg 1985; 64: 23–9

    PubMed  CAS  Google Scholar 

  178. Loft S, Egsmose C, Sonne J, et al. Metronidazole elimination is preserved in the elderly. Hum Exp Toxicol 1990; 9: 155–9

    PubMed  CAS  Google Scholar 

  179. Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 1984; 61: 27–35

    PubMed  CAS  Google Scholar 

  180. Frye RF, Matzke GR, Jallad NS, et al. The effect of age on the pharmacokinetics of the opioid antagonist nalmefene. Br J Clin Pharmacol 1996; 42: 301–6

    PubMed  CAS  Google Scholar 

  181. Lees KR, Green ST, Reid JL. Influence of age on the pharmacokinetics and pharmacodynamics of perindopril. Clin Pharmacol Ther 1988; 44: 418–25

    PubMed  CAS  Google Scholar 

  182. Ochs HR, Greenblatt DJ, Woo E, et al. Reduced quinidine clearance in elderly persons. Am J Cardiol 1978; 42: 481–5

    PubMed  CAS  Google Scholar 

  183. Greenblatt DJ, Abernethy DR, Boxenbaum HG, et al. Influence of age, gender, and obesity on salicylate kinetics following single doses of aspirin. Arthritis Rheum 1986; 29: 971–80

    PubMed  CAS  Google Scholar 

  184. Rowland M. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet 1990; 18: 184–209

    PubMed  CAS  Google Scholar 

  185. Edwards DY, Zarowitz BJ, Slaugther RL. Theophylline. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. 3rd ed. Vancouver (WA): Applied Therapeutics Inc., 1992: 13.1–13.38

    Google Scholar 

  186. Greenblatt DJ, Friedman H, Burstein ES, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther 1987; 42: 193–200

    PubMed  CAS  Google Scholar 

  187. Guay DR, Vance-Bryan K, Gilliland S, et al. Comparison of vancomycin pharmacokinetics in hospitalized elderly and young patients using a Bayesian forecaster. J Clin Pharmacol 1993; 33: 918–22

    PubMed  CAS  Google Scholar 

  188. Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. In press

  189. Greenblatt DJ, Divoll M, Abernethy DR, et al. Alprazolam kinetics in the elderly: relation to antipyrine disposition. Arch Gen Psychiatr 1983; 40: 287–90

    PubMed  CAS  Google Scholar 

  190. Sweet RA, Pollock BG, Kirshner M, et al. Pharmacokinetics of single- and multiple-dose bupropion in elderly patients with depression. J Clin Pharmacol 1995; 35: 876–84

    PubMed  CAS  Google Scholar 

  191. Somogyi A, Hewson D, Muirhead M, et al. Amiloride disposition in geriatric patients: importance of renal function. Br J Clin Pharmacol 1990; 29: 1–8

    PubMed  CAS  Google Scholar 

  192. Kaiser G, Ackermann R, Dieterle W, et al. Pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril in the elderly. Eur J Clin Pharmacol 1990; 38: 379–85

    PubMed  CAS  Google Scholar 

  193. Ochs HR, Greenblatt DJ, Friedman H, et al. Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol. Clin Pharmacol Ther 1987; 41: 562–70

    PubMed  CAS  Google Scholar 

  194. Miglioli PA, Pivetta P, Strazzabosco M, et al. Effect of age on single- and multiple-dose pharmacokinetics of erythromycin. Eur J Clin Pharmacol 1990; 39: 161–4

    PubMed  CAS  Google Scholar 

  195. Taburet AM, Devillers A, Thomare P, et al. Disposition of fleroxacin, a new trifluoro-quinolone, and its metabolites: pharmacokinetics in elderly patients. Clin Pharmacokinet 1990; 19: 80–8

    PubMed  CAS  Google Scholar 

  196. Jaber LA, Antal EF, Welshman IR. Pharmacokinetics and pharmacodynamics of glyburide in young and elderly patients with non-insulin-dependent diabetes mellitus. Ann Phar-macother 1996; 30: 472–5

    CAS  Google Scholar 

  197. Albert KS, Gillespie WR, Wagner JG, et al. Effects of age on the clinical pharmacokinetics of ibuprofen. Am J Med 1984; 77: 47–50

    PubMed  CAS  Google Scholar 

  198. Greenblatt DJ, Abernethy DR, Matlis R, et al. Absorption and disposition of ibuprofen in the elderly. Arthritis Rheum 1984; 27: 1066–9

    PubMed  CAS  Google Scholar 

  199. Hussein Z, Granneman GR, Mukherjee D, et al. Age-related differences in the pharmacokinetics and pharmacodynamics of lansoprazole. Br J Clin Pharmacol 1993; 36: 391–8

    PubMed  CAS  Google Scholar 

  200. Pieniaszek HJ Jr, Fiske WD, Saxton TD, et al. Single-dose pharmacokinetics, safety, and tolerance of linopirdine (DuP 996) in healthy young adults and elderly volunteers. J Clin Pharmacol 1995; 35: 22–30

    PubMed  CAS  Google Scholar 

  201. Chien SC, Chow AT, Natarajan J, et al. Absence of age and gender effects on the pharmacokinetics of a single 500 mg oral dose of levofloxacin in healthy subjects. Antimicrob Agents Chemother 1997; 41: 1562–5

    PubMed  CAS  Google Scholar 

  202. Sambol NC, Chiang J, Lin ET, et al. Kidney function and age are both predictors of pharmacokinetics of metformin. J Clin Pharmacol 1995; 35: 1094–102

    PubMed  CAS  Google Scholar 

  203. Stoeckel K, Pfefen JP, Mayersohn M, 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 

  204. Upton RA, Williams RL, Kelly J, et al. Naproxen pharmacokinetics in the elderly. Br J Pharmacol 1984; 18: 207–14

    CAS  Google Scholar 

  205. Barbhaiya RH, Buch AB, Greene DS. A study of the effect of age and gender on the pharmacokinetics of nefazodone after single and multiple doses. J Clin Psychopharmacol 1996; 16: 19–25

    PubMed  CAS  Google Scholar 

  206. Frydman A. Pharmacokinetic profile of nicorandil in humans: an overview. J Cardiovasc Pharmacol 1992; 20Suppl. 3: S34–44

    PubMed  CAS  Google Scholar 

  207. Greenblatt DJ, Abernethy DR, Locniskar A, et al. Age, sex, and nitrazepam kinetics: relation to antipyrine disposition. Clin Pharmacol Ther 1985; 38: 697–703

    PubMed  CAS  Google Scholar 

  208. Greenblatt DJ, Matalis R, Scavone JM, et al. Oxaprozin pharmacokinetics in the elderly. Br J Clin Pharmacol 1985; 19: 373–8

    PubMed  CAS  Google Scholar 

  209. van Heiningen PN, Eve MD, Oosterhuis B, et al. The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine. Clin Pharmacol Ther 1991; 50: 410–9

    PubMed  Google Scholar 

  210. Richardson CJ, Blocka KLN, Ross SG, et al. Effects of age and sex on piroxicam disposition. Clin Pharmacol Ther 1985; 37: 13–8

    PubMed  CAS  Google Scholar 

  211. Andros E, Detmar-Hanna D, Suteparuk S, et al. The effect of aging on the pharmacokinetics and pharmacodynamics of prazosin. Eur J Clin Pharmacol 1996; 50: 41–6

    PubMed  CAS  Google Scholar 

  212. Martines C, Gatti G, Sasso E, et al. The disposition of primidone in elderly patients. Br J Clin Pharmacol 1990; 30: 607–11

    PubMed  CAS  Google Scholar 

  213. Snoeck E, Van Peer A, Sack M, et al. Influence of age, renal and liver impairment on the pharmacokinetics of risperidone in man. Psychopharmacology 1995; 122: 223–9

    PubMed  CAS  Google Scholar 

  214. Wong SL, Cao GL, Mack RL, et al. Pharmacokinetics of sertindole in healthy young and elderly male and female subjects. Clin Pharmacol Ther 1997; 62: 157–64

    PubMed  CAS  Google Scholar 

  215. Ronfield RA, Tremaine LM, Wildner KD. Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers. Clin Pharmacokinet 1992; 32Suppl. 1: 22–30

    Google Scholar 

  216. Taggart AJ, McDermott BJ, Roberts SD. The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in patients with rheumatoid arthritis. Clin Pharmacokinet 1992; 23: 311–20

    PubMed  CAS  Google Scholar 

  217. Sitar DS, Warren CP, Aoki FY. Pharmacokinetics and pharmacodynamics of bambuterol, a long-acting bronchodilator pro-drug of terbutaline, in young and elderly patients with asthma. Clin Pharmacol Ther 1992; 52: 297–306

    PubMed  CAS  Google Scholar 

  218. Shah J, Teitelbaum P, Molony B, et al. Single and multiple dose pharmacokinetics of ticlopidine in young and elderly subjects. Br J Clin Pharmacol 1991; 32: 761–4

    PubMed  CAS  Google Scholar 

  219. Funcillo R, Troy S, Parker V, et al. Pharmacokinetics of the aldose reductase inhibitor tolrestat: studies in healthy young and elderly male and female subjects and in subjects with diabetes. Clin Pharmacol Ther 1996; 59: 603–12

    Google Scholar 

  220. Greenblatt DJ, Harmatz JS, Shapiro L, et al. Sensitivity to triazolam in the elderly. N Engl J Med 1991; 324: 1691–8

    PubMed  CAS  Google Scholar 

  221. Braekman RA, Granneman GR, Locke CS, et al. The pharmacokinetics of zileuton in healthy young and elderly volunteers. Clin Pharmacokinet 1995; 29Suppl. 2: 42–8

    Google Scholar 

  222. Spring P. Calculation of drug dosage regimens in patients with renal disease: a new nomographic method. Int J Clin Pharmacol Biopharm 1975; 11: 76–80

    PubMed  CAS  Google Scholar 

  223. Dettli L. Individualization of drug dosage in patients with renal disease. Med Clin North Am 1974; 58: 977–85

    PubMed  CAS  Google Scholar 

  224. Bennet WM. Guide to drug dosage in renal failure. Clin Pharmacokinet 1988; 15: 326–54

    Google Scholar 

  225. Matzke GR, Millikin SP. Influence of renal function and dialysis on drug disposition. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. 3rd ed. Vancouver (WA): Applied Therapeutics Inc., 1992: 8.1–8.49

    Google Scholar 

  226. Dettli L. Pharmakokinetische Daten für die Dosisanpassung. In: Sektion Klinische Pharmakologie, editor. Schweizerische Gesellschaft für Pharmakologie und Toxikologie, Grundlagen der Arzneitherapie. Basel: Dokumed AG, 1996: 13–21

    Google Scholar 

  227. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 15: 31–41

    Google Scholar 

  228. Galeazzi RL, Omar-Amberg C, Karlaganis G. N-acetyl-procainamide kinetics in the elderly. Clin Pharmacol Ther 1981; 29: 440–6

    PubMed  CAS  Google Scholar 

  229. Schleger SI, Paulus HE. Non-steroidal and analgesic therapy in the elderly. Clin Rheum Dis 1986; 12: 245–73

    Google Scholar 

  230. Pan HYM, Hoffman BB, Pershe RA, et al. Decline in β-adrenergic receptor-mediated vascular relaxation with aging in man. J Pharmacol Exp Ther 1986; 238: 802–7

    Google Scholar 

  231. Klein C, Hiath WR, Gerber JG, et al. Age does not alter human vascular and nonvascular β2-adrenergic responses to isoproterenol. Clin Pharmacol Ther 1988; 44: 573–8

    PubMed  CAS  Google Scholar 

  232. Ullah MI, Newman GB, Saunders KB. Influence of age on response to ipratropium and salbutamol in man. Thorax 1981; 36: 523–9

    PubMed  CAS  Google Scholar 

  233. Dauchot P, Gravenstein JS. Effects of atropine on the electrocardiogram in different age groups. Clin Pharmacol Ther 1971; 12: 274–80

    PubMed  CAS  Google Scholar 

  234. Kelliher GJ, Conahan ST. Changes in vagal activity and response to muscarinic receptor agonists with age. J Gerontol 1980; 45: 842–9

    Google Scholar 

  235. Shepherd AMM, Elfellah HS. Effect of age on muscarinic responses in the rat heart [abstract]. Clin Res 1984; 32: 862A

    Google Scholar 

  236. Fink RI, Kilternan DG, Griffin J, et al. Mechanism of insulin resistance in ageing. J Clin Invest 1983; 50: 1523–35

    Google Scholar 

  237. Chen MS, Hindson DA, Verstal RE. Hypoglycemic agents and the treatment of diabetes mellitus in the elderly. In: Swift LG, editor. Clinical pharmacology in the elderly. New York: Marcel Decker, 1987: 581–643

    Google Scholar 

  238. Oba K, Nakano H, Okazaki K. Mild glucose intolerance in the elderly. Nippon Rinsho 1996; 54: 2773–8

    PubMed  CAS  Google Scholar 

  239. Meneilly GS, Dawson K, Tessier D. Alterations in glucose metabolism in the elderly patient with diabetes. Diabetes Care 1993; 16: 1241–8

    PubMed  CAS  Google Scholar 

  240. Marker JC, Cryer PE, Clutter WE. Attenuated glucose recovery from hypoglycemia in the elderly. Diabetes 1992; 41: 671–8

    PubMed  CAS  Google Scholar 

  241. Brodows RG. Benefits and risks with glyburide and glipizide in elderly NIDDM patients. Diabetes Care 1992; 15: 75–80

    PubMed  CAS  Google Scholar 

  242. Jennings PE. Oral antihyperglycaemics: considerations in older patients with non insulin dependent diabetes mellitus. Drugs Aging 1997; 10: 323–31

    PubMed  CAS  Google Scholar 

  243. Irvine NA, Shepherd AMM. Age and blood pressure determine vasodepressor response to sodium nitroprusside. J Cardiovasc Pharmacol 1984; 6: 816–21

    PubMed  CAS  Google Scholar 

  244. Shammas E, Dickstein K. Drug selection for optimal treatment of hypertension in the elderly. Drugs Aging 1997; 11: 19–26

    PubMed  CAS  Google Scholar 

  245. Verhaeverbeeke I, Mets T. Drug induced orthostatic hypotension in the elderly. Drug Saf 1997; 17: 105–18

    Google Scholar 

  246. Schwartz JB. Calcium antagonist in the elderly. Drugs Aging 1996; 9: 24–36

    PubMed  CAS  Google Scholar 

  247. Shepherd AMM, Hewick DS, Moreland TA, et al. Age as a determinant of sensitivity to warfarin. Br J Pharmacol 1977; 4: 315–20

    CAS  Google Scholar 

  248. Routledge PA, Chapman PH, Davies DM, et al. Factors affecting warfarin requirements. Eur J Clin Pharmacol 1979; 15: 319–22

    PubMed  CAS  Google Scholar 

  249. Jones BR, Baran A, Reidenberg MM. Evaluating patients’ warfarin requirements. J Am Geriatr Soc 1980; 28: 10–12

    PubMed  CAS  Google Scholar 

  250. Reidenberg MM. Drug therapy in the elderly: the problem from the point of view of a clinical pharmacologist. Clin Pharmacol Ther 1987; 42: 677–80

    PubMed  CAS  Google Scholar 

  251. Feely J, Coakly D. Altered pharmacodynamics in the elderly. Clin Geriatr Med 1990; 6: 269–83

    PubMed  CAS  Google Scholar 

  252. Whitefield LR, Schentag JJ, Levy G. Relationship between concentration and anticoagulant effect of heparin in plasma of hospitalized patients: magnitude and predictability of inter-individual differences. Clin Pharmacol Ther 1982; 32: 503–16

    Google Scholar 

  253. Kimmick GG, Fleming R, Muss HB, et al. Cancer chemotherapy in older adults: a tolerability study. Drugs Aging 1997; 10: 34–49

    PubMed  CAS  Google Scholar 

  254. Horner TD, Stanski DR. The effect of increasing age on thiopental disposition and anesthesia requirements. Anesthesiology 1985; 62: 714–24

    Google Scholar 

  255. Avram M, Sanghui R, Henthorn TK, et al. Determinants of thiopental induction dose requirements. Anesth Analg 1993; 76: 10–17

    PubMed  CAS  Google Scholar 

  256. Jones AG, Hunter JM. Anaesthesia in the elderly, special considerations. Drugs Aging 1996; 9: 319–31

    PubMed  CAS  Google Scholar 

  257. Hetzel W. Antikonvulsive Behandlung im höheren Lebensalter — Grundlagen und Differentialindikation. Fortschr Neurol Psychiatr 1997; 65: 261–77

    PubMed  CAS  Google Scholar 

  258. Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age: a simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987; 240: 159–66

    PubMed  CAS  Google Scholar 

  259. Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil, model application. Anesthesiology 1997; 86: 24–33

    PubMed  CAS  Google Scholar 

  260. Ray WA, Federspiel CF, Schaffer W. A study of antipsychotic drug use in nursing homes: epidemiologic evidence suggesting misuse. Am J Public Health 1980; 70: 485–91

    PubMed  CAS  Google Scholar 

  261. Avorn J, Dreyer P, Connelly K, et al. Use of psychoactive medication and the quality of care in rest homes: findings and policy implications for a statewide study. N Engl J Med 1989; 320: 227–32

    PubMed  CAS  Google Scholar 

  262. Larson EB, Kukull WA, Buchner D, et al. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med 1987; 107: 169–73

    PubMed  CAS  Google Scholar 

  263. Morrison RL, Katz IR. Drug-related cognitive impairment: current progress and recurrent problems. Annu Rev Gerontol Geriatr 1989; 9: 232–84

    PubMed  CAS  Google Scholar 

  264. Ried LD, Johnson RE, Gettman OA. Benzodiazepine exposure and functional status in older people. J Am Geriatr Soc 1998; 46: 71–6

    PubMed  CAS  Google Scholar 

  265. Castleden CM, George CF, Marcer D, et al. Increased sensitivity to nitrazepam in old age. BMJ 1977; 1: 10–2

    PubMed  CAS  Google Scholar 

  266. Bressler R. Adverse drug reactions. In: Bressler R, Katz MD, editors. Geriatric Pharmacology. New York: McGraw-Hill, 1993: 41–61

    Google Scholar 

  267. Oxman TE. Antidepressants and cognitive impairment in the elderly. J Clin Psychiatry 1996; 57Suppl. 5: 38–44

    PubMed  Google Scholar 

  268. Zaleon CR, Guthrie SK. Antipsychotic drug use in older adults. Am J Hosp Pharm 1994; 51: 2917–43

    PubMed  CAS  Google Scholar 

  269. Livingstone RL, Zucker DK, Isenberg K, et al. Tricyclic antidepressants and delirium. J Clin Psychiatry 1983; 44: 173–6

    Google Scholar 

  270. Newhouse P. Use of serotonin selective reuptake inhibitors in geriatric depression. J Clin Psychiatry 1996; 57Suppl. 5: 12–22

    PubMed  CAS  Google Scholar 

  271. Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging 1993; 3: 335–48

    PubMed  CAS  Google Scholar 

  272. Heckbert SR, Longstreth WT, Psaty BM, et al. The association of antihypertensive agents with MRI white matter findings and with modified mental state examination in adults. J Am Geriatr Soc 1997; 45: 1423–33

    PubMed  CAS  Google Scholar 

  273. Ray WA, Griffin MR, Schaffner W, et al. Psychotropic drug use and the risk of hip fractures. N Engl J Med 1987; 316: 363–9

    PubMed  CAS  Google Scholar 

  274. Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA 1989; 262: 3303–7

    PubMed  CAS  Google Scholar 

  275. Cumming RG. Epidemiology of medication-related falls and fractures in the elderly. Drugs Aging 1998: 12: 43–53

    PubMed  CAS  Google Scholar 

  276. Mattson RH. Antiepileptic drug monitoring: a reappraisal. Epilepsia 1995; 36Suppl. 5: S22–9

    PubMed  Google Scholar 

  277. Zaske DE. Aminoglycosides. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. 3rd ed. Vancouver (WA): Applied Therapeutics Inc., 1992: 14.1–14.47

    Google Scholar 

  278. Lynch RA, Horowitz LN. Managing geriatric arrhythmias: II. Drug selection and use. Geriatrics 1991; 46: 41–4

    PubMed  CAS  Google Scholar 

  279. DeVane CL, Jarecke CR. Cyclic antidepressants. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetic. 3rd ed. Vancouver (WA): Applied Therapeutics Inc., 1992: 33.1–33–47

    Google Scholar 

  280. Schulz M, Schmoldt A. Zusammenstellung therapeutischer und toxischer Plasmakonzentrationen von Arzneistoffen. Anaesthesist 1994; 43: 835–44

    PubMed  CAS  Google Scholar 

  281. Benet LZ, Øie S, Schwartz JB. Design and optimization of dosage regimes; pharmacokinetic data. In: Hardman JG, Limbird LE, Molinoff PB, et al, editors. Goodman and Gil-man’s the pharmacological basis of therapeutics, 9th ed. New York: McGraw-Hill, 1996: 1707–92

    Google Scholar 

  282. Reynolds DJM, Aronson JK. ABC of monitoring drug therapy: making the most of plasma drug concentration measurements. BMJ 1993; 306: 48–51

    PubMed  CAS  Google Scholar 

  283. Spector R, Park GD, Johnson GF, et al. Therapeutic drug monitoring. Clin Pharmacol Ther 1988; 43: 345–53

    PubMed  CAS  Google Scholar 

  284. Tonkin AL, Bochner F. Therapeutic drug monitoring and patient outcome: a review of the issues. Clin Pharmacokinet 1994; 27: 169–74

    PubMed  CAS  Google Scholar 

  285. Campbell M. Community-based therapeutic drug monitoring: useful development or unnecessary distraction? Clin Pharmacokinet 1995; 28: 271–4

    PubMed  CAS  Google Scholar 

  286. von Harnack G-A, Janssen F. Pädiatrische Dosistabellen. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1989

    Google Scholar 

  287. Willmore LJ. The effect of age on the pharmacokinetics of anti-epileptic drugs. Epilepsia 1995; 36Suppl. 5: S14–S21

    PubMed  Google Scholar 

  288. Lewis DA, Reeves DS. Antibiotics at the extremes of age: choices and constraints. J Antimicrob Chemother 1994; 34Suppl. A: 11–8

    PubMed  Google Scholar 

  289. Bonetti A, Franceschi T, Apostoli P, et al. Cisplatin pharmacokinetics in elderly patients. Ther Drug Monit 1994; 16: 477–82

    PubMed  CAS  Google Scholar 

  290. Dahl SG. Plasma level monitoring of antipsychotic drugs: clinical utility. Clin Pharmacokinet 1986; 11: 36–61

    PubMed  CAS  Google Scholar 

  291. Putten T van, Marder SR, Hintz J, et al. Haloperidol plasma levels and clinical response: a therapeutic window relationship. Am J Psychiatry 1992; 149: 500–5

    PubMed  Google Scholar 

  292. Bocksberger JP, Gex-Fabry M, Gauthey L, et al. Clomipramine therapy in the geriatric hospital: experience with therapeutic drug monitoring. Ther Drug Monit 1994; 16: 113–9

    PubMed  CAS  Google Scholar 

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Turnheim, K. Drug Dosage in the Elderly. Drugs Aging 13, 357–379 (1998). https://doi.org/10.2165/00002512-199813050-00003

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Keywords

  • Adis International Limited
  • Therapeutic Drug Monitoring
  • Antipyrine
  • Zileuton
  • Fleroxacin