ADME-tox issues for the elderly

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 10, 2008, Pages 1321-1331

  Hilmer, Sarah N ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Absorption; Ageing; Distribution; Elderly; Excretion; Metabolism; Pharmacology; Toxicology

Indexed keywords

ALLYL ALCOHOL; AMITRIPTYLINE; AMPICILLIN; BENZODIAZEPINE DERIVATIVE; CHOLINERGIC RECEPTOR BLOCKING AGENT; DIAZEPAM; DICLOFENAC; ERYTHROPOIETIN; FENTANYL; GENTAMICIN; HEPARIN; HISTAMINE H2 RECEPTOR ANTAGONIST; INSULIN; INTERFERON; IRON; KETOCONAZOLE; METOCLOPRAMIDE; MIDAZOLAM; MORPHINE; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PHENYTOIN; PRODRUG; PROPRANOLOL; PROTON PUMP INHIBITOR; RISEDRONIC ACID; THEOPHYLLINE; UNINDEXED DRUG; VERAPAMIL; WARFARIN;

AREA UNDER THE CURVE; BALANCE IMPAIRMENT; BLEEDING; BODY POSTURE; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; COGNITIVE DEFECT; CONFUSION; DIGESTIVE SYSTEM PERFORATION; DOSE CALCULATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG FATALITY; DRUG METABOLISM; DRUG SAFETY; DRUG SENSITIVITY; ELDERLY CARE; GASTROINTESTINAL HEMORRHAGE; GERIATRIC PATIENT; GLOMERULUS FILTRATION RATE; HEALTH CARE COST; HUMAN; KIDNEY CLEARANCE; LIVER CLEARANCE; LIVER TOXICITY; NEPHROTOXICITY; NONHUMAN; PHARMACODYNAMICS; POLYPHARMACY; POSTURAL SWAY; REVIEW; SIDE EFFECT;

AGE FACTORS; AGED; AGING; DOSE-RESPONSE RELATIONSHIP, DRUG; FRAIL ELDERLY; HUMANS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; TISSUE DISTRIBUTION;

EID: 55049092764     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.4.10.1321     Document Type: Review

References (116)

1. Australian Institute of Health and Welfare. Use of health and aged care services. In: Older Australia at a glance. 4th edition. 2007
2. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Arch Intern Med 2007;167(16):1752-9
3. Gurwitz JH, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991;114(11):956-66
4. Saltzman JR, Kowdley KV, Perrone G, Russell RM. Changes in small-intestine permeability with aging. J Am Geriatr Soc 1995;43(2);160-4
5. Yuasa H, Soga N, Kimura Y, Watanabe J. Effect of aging on the intestinal transport of hydrophilic drugs in the rat small intestine. Biol Pharm Bull 1997;20(11):1188-92
6. Hollander D, Tarnawski H. Aging-associated increase in intestinal absorption of macromolecules. Gerontology 1985;31(3):133-7
7. Drozdowski L, Thomson AB. Aging and the intestine. World J Gastroenterol 2006;12(47):7578-84
8. Armbrecht HJ, Boltz MA, Kumar VB. Intestinal plasma membrane calcium pump protein and its induction by 1,25(OH)2;D3; decrease with age. Am J Physiol 1999;277(1 Pt 1):G41-47
9. Toyoshima M, Inada M, Kameyama M. Effects of aging on intracellular transport of vitamin B12 (B12) in rat enterocytes. J Nutr Sci Vitaminol (Tokyo) 1983;29(1):1-10
10. O'Mahony D, O'Leary P, Quigley EM. Aging and intestinal motility: a review of factors that affect intestinal motility in the aged. Drugs Aging 2002;19(7):515-27
11. Hurwitz A, Brady DA, Schaal SE, et al. Gastric acidity in older adults. JAMA 1997;278(8);659-62
12. Wilkinson GR. The effects of diet, aging and disease-states on presystemic elimination and oral drug bioavailability in humans. Adv Drug Deliv Rev 1997;27(2-3):129-59
13. Hughes VA, Roubenoff R, Wood M, et al. Anthropometric assessment of 10-y changes in body composition in the elderly. Am J Clin Nutr 2004;80(2):475-82
14. Warrington JS, Greenblatt DJ, von Moltke LL. The effect of age on P-glycoprotein expression and function in the Fischer-344 rat. J Pharmacol Exp Ther 2004;309(2):730-6
15. Toornvliet R, van Berckel BN, Luurtsema G, et al. Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[11;C]verapamil and positron emission tomography. Clin Pharmacol Ther 2006;79(6);540-8
16. Payne GW, Bearden SE. The microcirculation of skeletal muscle in aging. Microcirculation 2006;13(4):275-7
17. Nnodim JO. Stereological assessment of age-related changes in lipid droplet surface area and vascular volume in rat interscapular brown adipose tissue. Anat Rec 1988;220(4):57-63
18. Coin A, Sergi G, Minicuci N, et al. Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80 year-old Italian population. Clin Nutr 2008;27(1):87-94
19. Hughes VA, Frontera WR, Wood M, et al. Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol A Biol Sci Med Sci 2001;56(5);B209-217
20. Cesari M, Leeuwenburgh C, Lauretani F, et al. Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin Nutr 2006;83(5):1142-8
21. McLean AJ, Le Coureur DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev 2004;56(2):163-84
22. Le Couteur DG, McLean AJ. The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet 1998;34(5):359-73
23. Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging 2001;18(11):837-51
24. Butler JM, Begg EJ. Free drug metabolic clearance in elderly people. Clin Pharmacokinet 2008;47(5):297-321
25. Schwartz JB. Erythromycin breath test results in elderly, very elderly, and frail elderly persons. Clin Pharmacol Ther 2006;79(5):440-8
26. Wynne HA, Yelland C, Cope LH, et al. The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide. Age Ageing 1993;22(5):354-9
27. Wynne HA, Cope LH, Herd B, et al. The association of age and frailty with paracetamol conjugation in man. Age Ageing 1990;19(6):419-24
28. Williams FM, Wynne H, Woodhouse KW, Rawlins MD. Plasma aspirin esterase: the influence of old age and frailty. Age Ageing 1989;18(1):39-42
29. Fliser D. Ren sanus in corpore sano: the myth of the inexorable decline of renal function with senescence. Nephrol Dial Transplant 2005;20(3):482-5
30. Englund G, Hallberg P, Artursson P, et al. Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring. BMC Med 2004;2:8
31. Reidenberg MM, Camacho M, Kluger J, Drayer DE. Aging and renal clearance of procainamide and acetylprocainamide. Clin Pharmacol Ther 1980;28(6):732-5
32. Sproule BA, Hardy BG, Shulman KI. Differential pharmacokinetics of lithium in elderly patients. Drugs Aging 2000;16(3):65-77
33. Muhlberg W, Platt D. Age-dependent changes of the kidneys: pharmacological implications. Gerontology 1999;45(5):243-53
34. Spring P. Calculation of drug dosage regimens in patients with renal disease: a new nomographic method. Int J Clin Pharmacol Biopharm 1975;11(1):76-80
35. Tumheim K. Pitfalls of pharmacokinetic dosage guidelines in renal insufficiency. Eur J Clin Pharmacol 1991;40(1):87-93
36. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41
37. Triggs E, Charles B. Pharmacokinetics and therapeutic drug monitoring of gentamicin in the elderly. Clin Pharmacokinet 1999;37(4):331-41
38. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130(6):461-70
39. Gill J, Malyuk R, Djurdjev O, Levin A. Use of GFR equations to adjust drug doses in an elderly multi-ethnic group - a cautionary tale. Nephrol Dial Transplant 2007;22(10):2894-9
40. Burkhardt H, Bojarsky G, Gretz N, Gladisch R. Creatinine clearance, Cockcroft-Gault formula and cystatin C: estimators of true glomerular filtration rate in the elderly? Gerontology 2002;48(3):140-6
41. Bowie MW, Slattum PW. Pharmacodynamics in older adults: a review. Am J Geriatr Pharmacother 2007;5(3):263-303
42. White M, Roden R, Minobe W, et al. Age-related changes in beta-adrenergic neuroeffector systems in the human heart. Circulation 1994;90(3):1225-38
43. Abernethy DR, Schwartz JB, Plachetka JR, et al. Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension. Am J Cardiol 1987;60(8):697-702
44. 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(1):76-86
45. Montamat SC, Abernethy DR. Calcium antagonists in geriatric patients: diltiazem in elderly persons with hypertension. Clin Pharmacol Ther 1989;45(6):682-91
46. Ford GA, Hoffman BB, Vestal RE, Blaschke TF. Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man. Br J Clin Pharmacol 1992;33(1):83-7
47. Albrecht S, Ihmsen H, Hering W, et al. The effect of age on the pharmacokinetics and pharmacodynamics of midazolam. Clin Pharmacol Ther 1999;65(6):630-9
48. Swift CG, Swift MR, Ankier SI, et al. Single dose pharmacokinetics and pharmacodynamics of oral loprazolam in the elderly. Br J Clin Pharmacol 1985;20(2):119-28
49. Sorock GS, Shimkin EE. Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Arch Intern Med 1988;148(11):2441-4
50. Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987;240(1):159-66
51. Schnider TW, Minto CF, Shafer SL, et al. The influence of age on propofol pharmacodynamics. Anesthesiology 1999;90(6):1502-16
52. Kurtovic J, Riordan SM. Paracetamol-induced hepatotoxicity at recommended dosage. J Intern Med 2003;253(2);240-3
53. Purser JL, Kuchibhada MN, Fillenbaum GG, et al. Identifying frailty in hospitalized older adults with significant coronary artery disease. J Am Geriatr Soc 2006;54(11):1674-81
54. Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 2002;162(20):2333-41
55. Robin DW, Hasan SS, Edeki T, et al. Increased baseline sway contributes to increased losses of balance in older people following triazolam. J Am Geriatr Soc 1996;44(3):300-4
56. Vijayan VK. Cholinergic enzymes in the cerebellum and the hippocampus of the senescent mouse. Exp Gerontol 1977;12(1-2):7-11
57. White P, Hiley CR, Goodhardt MJ, et al. Neocortical cholinergic neurons in elderly people. Lancet 1977;180(13):668-71
58. Sunderland T, Tariot PN, Cohen RM, et al. Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls. A dose-response study. Arch Gen Psychiatry 1987;44(5):418-26
59. Rikans LE. Influence of aging on chemically induced hepatotoxicity: role of age-related changes in metabolism. Drug Metab Rev 1989;20(1):87-110
60. Rikans LE, Cai Y, Kosanke SD, Venkataraman PS. Redox cycling and hepatotoxicity of diquat in aging male Fischer 344 rats. Drug Metab Dispos 1993;21(4):605-10
61. Hilmer SN, Cogger VC, Le Couteur DG. Basal activity of Kupffer cells increases with old age. J Gerontol A Biol Sci Med Sci 2007;62(9):973-8
62. Yamano T, DeCicco LA, Rikans LE. Attenuation of cadmium-induced liver injury in senescent male fischer 344 rats: role of Kupffer cells and inflammatory cytokines. Toxicol Appl Pharmacol 2000;162(1):68-75
63. Holt MP, Ju C. Mechanisms of drug-induced liver injury. AAPS J 2006;8(1):E48-54
64. Warner HR. Aging and regulation of apoptosis. Curr Top Cell Regul 1997;35:107-21
65. Kujoth GC, Hiona A, Pugh TD, et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005;309(5733):481-4
66. Kim YC, Kim SY, Sohn YR. Effect of age increase on metabolism and toxicity of ethanol in female rats. Life Sci 2003;74(4);509-19
67. Mallikarjuna K, Nishanth K, Reddy KS. Hepatic glutathione mediated antioxidant system in ethanol treated rats: decline with age. Pathophysiology 2007;14(1):17-21
68. Walker J, Wynne H. Review: the frequency and severity of adverse drug reactions in elderly people. Age Ageing 1994;23(3):255-9
69. Beyth RJ, Short RI. Epidemiology of adverse drug reactions in the elderly by drug class. Drugs Aging 1999;14(3);231-9
70. Bordet R, Gautier S, Le Louet H, et al. Analysis of the direct cost of adverse drug reactions in hospitalised patients. Eur J Clin Pharmacol 2001;56(12):935-41
71. Carbonin P, Pahor M, Bernabei R, Sgadari A. Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? J Am Geriatr Soc 1991;39(11):1093-9
72. Hurwitz N. Predisposing factors in adverse reactions to drugs. Br Med J 1969;1(643):536-9
73. Kellaway GS, McCrae E. Intensive monitoring for adverse drug effects in patients disease from acute medical wards. N Z Med J 1973;78(505):525-8
74. Pouyanne P, Haramburu F. Imbs JL, Begaud B. Admissions to hospital caused by adverse drug reactions: cross sectional incidence study. French Pharmacovigilance Centres. BMJ 2000;320(7241):1036
75. Routledge PA, O'Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol 2004;57(2):121-6
76. Atkin PA, Veitch PC, Veitch EM, Ogle SJ. The epidemiology of serious adverse drug reactions among the elderly. Drugs Aging 1999;14(2):141-52
77. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5
78. Mjorndal T, Boman MD, Hagg S, et al. Adverse drug reactions as a cause for admissions to a department of internal medicine. Pharmacoepidemiol Drug Saf 2002;11(1):65-72
79. Mannesse CK, Derkx FH, de Ridder MA, et al. Contribution of adverse drug reactions to hospital admission of older patients. Age Ageing 2000;29(1):35-9
80. Einarson TR. Drug-related hospital admissions. Ann Pharmacother 1993;27(7-8):832-40
81. Atkin PA, Shenfield GM. Medication-related adverse reactions and the elderly: a literatare review. Adverse Drug React Toxicol Rev 1995;14(3):175-91
82. Bootman JL, Harrison DL, Cox E. The health care cost of drug-related morbidity and mortality in nursing facilities. Arch Intern Med 1997;157(18):2089-96
83. Burgess CL, Holman CD, Satti AG. Adverse drug reactions in older Australians, 1981-2002. Med J Aust 2005;182(6):267-70
84. Moore RD, Smith CR, Lipsky JJ, et al. Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med 1984;100(3):352-7
85. McMartin DN, Engel SG. Effect of aging on gentamicin nephrotoxicity and pharmacokinetics in rats. Res Commun Chem Pathol Pharmacol 1982;38(2):193-207
86. Chan M, Nicklason F, Vial JH. Adverse drug events as a cause of hospital admission in the elderly. Intern Med J 2001;31(4):199-205
87. Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004;329(7456):15-9
88. Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/ perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med 2000;160(14):2093-9
89. Gurwitz JH, Avorn J, Bohn RL, et al. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA 1994;272(10):781-6
90. Johnson AG. NSAIDs and blood pressure. Clinical importance for older patients. Drugs Aging 1998;12(1):17-27
91. Henry D, Page J, Whyte I, et al. Consumption of non-steroidal anti-inflammatory drugs and the development of functional renal impairment in elderly subjects. Results of a case-control study. Br J Clin Pharmacol 1997;44(1):85-90
92. Banks AT, Zimmerman HJ, Ishak KG, Harter JG. Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions. Hepatology 1995;22(3):820-7
93. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370(9586):493-503
94. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115(21):2689-96
95. Gurwitz JH, Field TS, Radford MJ, et al. The safety of warfarin therapy in the nursing home setting. Am J Med 2007;120(6):539-44
96. Anderson G, Kerluke K. Distribution of prescription drug exposures in the elderly: description and implications. J Clin Epidemiol 1996;49(8):929-35
97. Jorgensen T, Johansson S, Kennerfalk A, et al. Prescription drug use, diagnoses, and healthcare utilization among the elderly. Ann Pharmacother 2001;35(9):1004-9
98. Kennerfalk A, Ruigomez A, Wallander MA, et al. Geriatric drug therapy and healthcare utilization in the United kingdom. Ann Pharmacother 2002;36(5):797-803
99. Sorensen L, Stokes JA, Purdie DM, et al. Medication management at home: medication-related risk factors associated with poor health outcomes. Age Ageing 2005;34(6):626-32
100. Simons LA, Tett S, Simons J, et al. Multiple medication use in the elderly. Use of prescription and non-prescription drugs in an Australian community setting. Med J Aust 1992;157(4):242-6
101. Cohen RJ, Ek K, Pan CX. Complementary and alternative medicine (CAM) use by older adults: a comparison of self-report and physician chart documentation. J Gerontol A Biol Sci Med Sci 2002;57(4):M223-227
102. Flaherty JH, Takahashi R. The use of complementary and alternative medical therapies among older persons around the world. Clin Geriatr Med 2004;20(2):179-200
103. Bressler R. Herb-drug interactions: interactions between Ginkgo biloba and prescription medications. Geriatrics 2005;60(4):30-3
104. MacLennan AH, Wilson DH, Taylor AW. Prevalence and cost of alternative medicine in Australia. Lancet 1996;347(9001):569-73
105. Hoblyn JC, Brooks JO III. Herbal supplements in older adults. Consider interactions and adverse events that may result from supplement use. Geriatrics 2005;60(2):18,22-13
106. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med 2003;163(22):2716-24
107. Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ 1997;315(7115):1096-9
108. Kuijpers MA, van Marum RJ, Egberts AC, Jansen PA. Relationship between polypharmacy and underprescribing. Br J Clin Pharmacol 2008;65(1):130-3
109. Campbell AJ, Robertson MC, Gardner MM, et al. Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial. J Am Geriatr Soc 1999;47(7):850-3
110. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008;168(5):508-13
111. Cao YJ, Mager DE, Simonsick EM, et al. Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women. Clin Pharmacol Ther 2008;83(3):422-9
112. Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med 2007;167(8):781-7
113. Lanch F, Russo A, Liperoti R, et al. Anticholinergic drugs and physical unction among frail elderly population. Clin Pharmacol Ther 2007;81(2):235-41
114. Gray SL, LaCroix AZ, Hanlon JT, et al. Benzodiazepine use and physical disability in community-dwelling older adults. J Am Geriatr Soc 2006;54(2):224-30
115. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56(3):M146-156
116. Rockwood K, Andrew M, Mitnitski A. A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci 2007;62(7):738-43