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
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
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
Tumer N, Scarpace PJ, Lowenthal DT. Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 1992; 32: 271–302
Gosney M, Tillis R. Prescription of contraindicated and interacting drugs in elderly patients admitted to hospital. Lancet 1984; II: 564–7
Adams KHR, Al-Hamouz S, Edmund E. Inappropriate prescribing in the elderly. J R Coll Physicians Lond 1987; 21: 39–41
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
Grymonpre RE, Mitenko PA, Sitar DS, et al. Drug associated hospital admittances in older medical patients. J Am Geriatr Soc 1988; 36: 1092–8
Beard K. Adverse reactions as a cause of hospital admission in the aged. Drugs Aging 1992; 2: 356–67
Klein-Schwartz W, Oderda GM. Poisoning in the elderly: epidemiological, clinical and management considerations. Drugs Aging 1991; 1: 67–89
Do doctors short-change old people [editorial]? Lancet 1993; 342: 1–2
Wetle T. Age as a risk factor for inadequate treatment. JAMA 1987; 258: 516
Forman DE, Rich MW. Management of acute myocardial infarction in the elderly. Drugs Aging 1996; 8: 358–77
Gurwitz JH, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991; 114: 956–66
Shaw AB. Age as a basis for health care rationing: support for agist policies. Drugs Aging 1996; 9: 403–5
Birnbaum LS. Pharmacokinetic basis of age-related changes in sensitivity to toxicants. Annu Rev Pharmacol 1991; 31: 101–28
World Health Organization: health care in the elderly. Drugs 1981; 22: 279–94
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
Hauptverband der Sozialversicherungsträger in Österreich. Medikamentenerfassung. ÖSTAT 1994
Baum C, Kennedy DL, Forbes MB, et al. Drug use in the United States in 1981. JAMA 1981; 251: 1293–7
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
Tregaskis BF, Stevenson IH. Pharmacokinetics in old age. Br Med Bull 1990; 46: 9–21
Ruiz JG, Array S, Lowenthal DT. Therapeutic drug monitoring in the elderly. Am J Ther 1996; 3: 839–60
Morrow D, Leirer V, Sheik J. Adherence and medication instructions: review and recommendations. J Am Geriatr Soc 1988; 36: 1147–60
Cramer JA. Enhancing patient compliance in the elderly: role of packaging aids and monitoring. Drugs Aging 1998; 12: 7–15
Dice JF. Cellular and molecular mechanisms of aging. Physiol Rev 1993; 73: 149–59
Knight JA. The process and theories of aging. Ann Clin Lab Sci 1995; 25: 1–12
Masoro EJ. Aging: current concepts. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 3–21
Kipling D, Faragher RGA. Progeroid syndromes: probing the molecular basis of aging. J Clin Pathol Mol Pathol 1997; 50: 234–41
Dyer CAE, Sinclair AJ. The premature aging syndromes: insights into the aging process. Age Aging 1998; 27: 73–80
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
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
Gafni A. Structural modifications of proteins during aging. J Am Geriatr Soc 1997; 45: 871–80
Miller RA. When will the biology of aging become useful? Future landmarks in biomedical gerontology. J Am Geriatr Soc 1997; 45: 1258–67
Yu BP. Putative interventions. In: Masoro EJ, editor. Handbook of physiology, sect. II: aging. New York: Oxford University Press, 1995: 613–31
Lamy PP. Physiological changes due to age; pharmacodynamic changes of drug action and implications for therapy. Drugs Aging 1991; 1: 385–404
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
Crockford PM, Harbeck RJ, Williams RM. Influence of age on intravenous glucose tolerance and serum immunoreactive insulin. Lancet 1966; I: 465–7
Lund-Johansen P. The hemodynamics of the aging cardiovascular system. J Cardiovasc Pharmacol 1988; 12Suppl. 8: S20–32
Cody RJ. Physiological changes due to age: implications for drug therapy of congestive heart failure. Drugs Aging 1993; 3: 322–34
Lakatta EG. Cardiovascular system. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 413–74
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
Docherty JR. Aging and the cardiovascular system. J Auton Pharmacol 1986; 6: 77–84
Docherty JR. Cardiovascular responses in ageing. Pharmacol Rev 1990; 42: 103–25
Folkow B, Svanborg A. Physiology of cardiovascular aging. Physiol Rev 1993; 73: 725–64
Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 1993; 73: 413–67
Sparrow D, Weiss ST. Respiratory system. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 475–83
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
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
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
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
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
Lindeman RD. Renal and urinary tract. In: Masoro EJ, editor. Handbook of physiology. Sect 11: aging. New York: Oxford University Press, 1995: 485–503
Kampmann J, Siersbaeck-Nielsen K, Kristensen M, et al. Rapid evaluation of creatinine clearance. Acta Med Scand 1974; 196: 517–20
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
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
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
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
Schmucker DL. Aging and drug disposition: an update. Pharmacol Rev 1985; 37: 133–48
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
O’Mahony MS, Woodhouse KW. Age, environmental factors and drug metabolism. Pharmacol Ther 1994; 61: 279–87
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
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
Hunt CM, Strater S, Stave GM. Effect of normal aging on the activity of human hepatic cytochrome P450IIE1. Biochem Pharmacol 1991; 40: 1666–9
Hunt CM, Westerkam WR, Stave FM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 1992; 44: 275–83
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
Roth GS. Hormone receptor changes during adulthood and senescence: significance for aging research. Fed Proc 1979; 38: 1910–4
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
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
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
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
Stuck AE, Frey BM, Frey FJ. Kinetics of prednisolone and endogenous cortisol suppression in the elderly. Clin Pharmacol Ther 1988; 43: 354–62
Wilkinson CN, Peskind ER, Raskind MA. Decreased hypothalamic pituitary adrenal axis sensitivity to cortisol feedback inhibition in human aging. Neuroendocrinology 1997; 65: 79–90
Yu S, Abel L, Globerson A. Thymocyte progenitors and T cell development in aging. Mech Ageing Dev 1997; 94: 103–11
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
Biasi D, Carletto A, Dellagnola C, et al. Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 1996; 20: 673–81
Rothstein G. Hematopoiesis in the aged: a model of hematopoietic dysregulation? Blood 1993; 82: 2601–4
Chatta GS, Dale DC. Aging and haematopoiesis: implications for treatment with thrombopoietic growth factors. Drugs Aging 1996; 9: 37–47
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
Muravchik S. Immediate and long term nervous system effects of anesthesia in elderly patients. Clin Anesth 1988; 4: 1035–45
Muravchik S. Anesthesia for the elderly. In: Miller R, editor. Anaesthesia. Edinburgh: Churchill Livingstone, 1994: 2143–56
Finch CE. Neuron atrophy during aging: programmed or sporadic. Trends Neurosci 1993; 16: 104–10
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
Katzman R. Human nervous system. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 325–44
Swift CG. Pharmacodynamics: changes in homeostatic mechanisms, receptor and target sensitivity in the elderly. Br Med Bull 1990; 46: 36–52
Catterson ML, Preskorn SH, Martin RL. Pharmacodynamic and pharmacokinetic considerations in geriatric psychopharmacology. Psychiatr Clin North Am 1997; 20: 205–18
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
Vestal R, Wood A, Shand D. Reduced β-adrenoreceptor sensitivity in the elderly. Clin Pharmacol Ther 1979; 26: 181–6
White M, Roden R, Minobe W, et al. Age-related changes in β-adrenergic neuroeffector systems in human heart. Circulation 1994; 90: 1225–38
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
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
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
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
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
Tanner C. Epidemiology of Parkinson’s disease. Neurol Clin 1992; 10: 317–28
Lanius RA, Pasqualotto BA, Shaw CA. Age-dependent expression, phosphorylation and function of neurotransmitter receptors: pharmacological implications. Trends Pharmacol Sci 1993; 14: 403–8
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
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
Renganathan M, Messi ML, Delbono O. Dihydropyridine receptor — ryanodine receptor uncoupling in aged skeletal muscle. J Membr Biol 1997; 157: 247–53
Obeid LM, Venable ME. Signal transduction in cellular senescence. J Am Geriatr Soc 1997; 45: 361–6
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
Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med 1989; 321: 303–9
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
Hymans DE. The elderly patient: a special case for diuretic therapy. Drugs 1986; 31Suppl. 4: 138–53
Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly. Clin Pharmacol Ther 1995; 57: 42–51
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
Durnas C, Loi CH, Cusack BY. Hepatic drug metabolism and aging. Clin Pharmacokinet 1990; 19: 359–89
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
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
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
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
Annesley T. Special considerations for geriatric therapeutic drug monitoring. Clin Chem 1989; 35: 1337–41
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
Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics of indomethacin in the elderly. Clin Pharmacokinet 1993; 24: 428–34
Bernus I, Dickinson RG, Hooper WD, et al. Anticonvulsant therapy in aged patients: clinical pharmacokinetic considerations. Drugs Aging 1997; 10: 278–89
Greenblatt DY, Shader RI, Harmatz JS. Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacol 1989; 29: 866–72
Advenier C, Saint-Aubin A, Gobert C, et al. Pharmacokinetics of isoniazid in the elderly. Br J Clin Pharmacol 1980; 10: 167–8
Gachalyi B, Vas A, Hajos P, et al. Acetylator phenotypes: effect of age. Eur J Clin Pharmacol 1984; 26: 43–5
Castleden CM, George CF. The effect of ageing on the hepatic clearance of propranolol. Br J Clin Pharmacol 1979; 7: 49–54
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
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
Rosenkranz B, Winkelmann BR, Parnham MJ. Clinical pharmacokinetics of molsidomine. Clin Pharmacokinet 1996; 30: 372–84
Kelly JG, McGarry K, O’Malley K, et al. Bioavailability of labetalol increases with age. Br J Clin Pharmacol 1982; 14: 304–5
Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol 1983; 5: 1093–6
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
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
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
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
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
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
Williams FM, Wynne H, Woodhouse KW, et al. Plasma aspirin esterase: the influence of old age and frailty. Age Ageing 1989; 18: 39–42
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
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
Wallace SM, Verbeek RK. Plasma protein binding of drugs in the elderly. Clin Pharmacokinet 1987; 12: 41–72
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
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
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
Campion EW, Avorn J, Reder VA, et al. Overmedication of low-weight elderly. Arch Intern Med 1987; 147: 945–7
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
Holt PR. The gastrointestinal tract. In: Masoro EJ, editor. Handbook of physiology. Sect. 11: aging. New York: Oxford University Press, 1995: 505–54
Majumdar APN, Fligiel SEG, Jaszewski R. Gastric mucosal injury and repair: effect of aging. Histol Histopathol 1997; 12: 491–501
Johnson SL, Mayersohn M, Conrad KA. Xylose disposition in humans as a function of age. Clin Pharmacol Ther 1986; 39: 697–702
Yoshikawa TT, Norman DC. Treatment of infections in elderly patients. Med Clin North Am 1995; 79: 651–61
Rubin PC, Scott PYW, Reid JL. Prazosin disposition in young and elderly subjects. Br J Clin Pharmacol 1981; 12: 401–4
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
Goa KL, Sorkin EM. Gabapentin: a review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993; 46: 409–27
Roskos KV, Maibach HI. Percutaneous absorption and age. Drugs Aging 1992; 2: 432–49
Roskos KV, Maibach HI, Guy RA. The effect of aging on percutaneous absorption in man. J Pharmacokinet Biopharm 1989; 17: 617–30
Turnheim K. Pitfalls in pharmacokinetic dosage guidelines in renal insufficiency. Eur J Clin Pharmacol 1991; 40: 87–93
Divoll M, Abernethy MA, Ameer B, et al. Acetaminophen kinetics in the elderly. Clin Pharmacol Ther 1982; 31: 151–6
Lemmens HJM, Burm AGL, Hennis PJ, et al. Influence of age on the pharmacokinetics of alfentanil: gender dependence. Clin Pharmacokinet 1990; 19: 416–22
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
Vanhaevenbeek M, Siska G, Herchuelz A. Pharmacokinetics of once-daily amikacin in elderly patients. J Antimicrob Chemother 1993; 31: 185–7
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
Schulz P, Turner-Tamiyasu K, Smith G, et al. Amitriptyline disposition in young and elderly normal men. Clin Pharmacol Ther 1983; 33: 360–6
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
Ornstein E, Lien CA, Matteu RS, et al. Pharmacodynamics and pharmacokinetics of cis-atracurium in geriatric surgical patients. Anesthesiology 1996; 84: 520–5
Barbhaiya RH, Knupp CA, Pittman KA. Effects of age and gender on pharmacokinetics of cefepime. Antimicrob Agents Chemother 1992; 36: 1181–5
Blouin RA, Stoeckel K. Cefetamet pivoxil clinical pharmacokinetics. Clin Pharmacokinet 1993; 25: 172–88
Greenblatt DJ, Divoll MK, Abernethy DR, et al. Age and gender effects of chlordiazepoxide kinetics: relation to antipyrine disposition. Pharmacology 1989; 38: 327–34
Nilsson-Ehle I, Ljunberg B. Quinolone disposition in the elderly: practical implications. Drugs Aging 1991; 1: 279–88
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
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
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
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
Silverberg PA, Matteo RS, Ornstein E, et al. Pharmacokinetics and pharmacodynamics of edrophonium in the elderly [abstract]. Anesth Analg 1986; 65 Suppl.: S142
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
Echizen H, Ishizaki T. Clinical pharmacokinetics of famotidine. Clin Pharmacokinet 1991; 21: 178–94
Blychert E, Edgar B, Elmfeldt D, et al. A population study of the pharmacokinetics of felodipine. Br J Clin Pharmacol 1991; 31: 15–24
Singleton MA, Rosen JI, Fisher DM. Pharmacokinetics of fentanyl in the elderly. Br J Anaesth 1988; 60: 619–22
Roncari G, Timm U, Zell M, et al. Flumazenil kinetics in the elderly. Eur J Clin Pharmacol 1993; 45: 585–7
Andreasen F, Hansen N, Husted SE, et al. The pharmacokinetics of furosemide are influenced by age. Br J Clin Pharmacol 1983; 16: 391–7
El-Sayed YM, Islam SI. Effect of age and renal function on gentamicin pharmacokinetic parameters. Int J Clin Pharmacol 1989; 27: 503–9
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
Abernethy DR, Greenblatt DJ, Shader RI. Imipramine and desipramine disposition in the elderly. J Pharmacol Exp Ther 1985; 232: 183–8
Greenblatt DJ, Divoll Allen M, Locniskar A, et al. Lorazepam kinetics in the elderly. Clin Pharmacol Ther 1979; 26: 103–13
Tornatore KM, Logue G, Venuto RC, et al. Pharmacokinetics of methylprednisolone in young and elderly males. J Am Geriatr Soc 1994; 42: 1118–22
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
Loft S, Egsmose C, Sonne J, et al. Metronidazole elimination is preserved in the elderly. Hum Exp Toxicol 1990; 9: 155–9
Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 1984; 61: 27–35
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
Lees KR, Green ST, Reid JL. Influence of age on the pharmacokinetics and pharmacodynamics of perindopril. Clin Pharmacol Ther 1988; 44: 418–25
Ochs HR, Greenblatt DJ, Woo E, et al. Reduced quinidine clearance in elderly persons. Am J Cardiol 1978; 42: 481–5
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
Rowland M. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet 1990; 18: 184–209
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
Greenblatt DJ, Friedman H, Burstein ES, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther 1987; 42: 193–200
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
Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. In press
Greenblatt DJ, Divoll M, Abernethy DR, et al. Alprazolam kinetics in the elderly: relation to antipyrine disposition. Arch Gen Psychiatr 1983; 40: 287–90
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
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
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
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
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
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
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
Albert KS, Gillespie WR, Wagner JG, et al. Effects of age on the clinical pharmacokinetics of ibuprofen. Am J Med 1984; 77: 47–50
Greenblatt DJ, Abernethy DR, Matlis R, et al. Absorption and disposition of ibuprofen in the elderly. Arthritis Rheum 1984; 27: 1066–9
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
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
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
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
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
Upton RA, Williams RL, Kelly J, et al. Naproxen pharmacokinetics in the elderly. Br J Pharmacol 1984; 18: 207–14
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
Frydman A. Pharmacokinetic profile of nicorandil in humans: an overview. J Cardiovasc Pharmacol 1992; 20Suppl. 3: S34–44
Greenblatt DJ, Abernethy DR, Locniskar A, et al. Age, sex, and nitrazepam kinetics: relation to antipyrine disposition. Clin Pharmacol Ther 1985; 38: 697–703
Greenblatt DJ, Matalis R, Scavone JM, et al. Oxaprozin pharmacokinetics in the elderly. Br J Clin Pharmacol 1985; 19: 373–8
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
Richardson CJ, Blocka KLN, Ross SG, et al. Effects of age and sex on piroxicam disposition. Clin Pharmacol Ther 1985; 37: 13–8
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
Martines C, Gatti G, Sasso E, et al. The disposition of primidone in elderly patients. Br J Clin Pharmacol 1990; 30: 607–11
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
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
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
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
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
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
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
Greenblatt DJ, Harmatz JS, Shapiro L, et al. Sensitivity to triazolam in the elderly. N Engl J Med 1991; 324: 1691–8
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
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
Dettli L. Individualization of drug dosage in patients with renal disease. Med Clin North Am 1974; 58: 977–85
Bennet WM. Guide to drug dosage in renal failure. Clin Pharmacokinet 1988; 15: 326–54
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
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
Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 15: 31–41
Galeazzi RL, Omar-Amberg C, Karlaganis G. N-acetyl-procainamide kinetics in the elderly. Clin Pharmacol Ther 1981; 29: 440–6
Schleger SI, Paulus HE. Non-steroidal and analgesic therapy in the elderly. Clin Rheum Dis 1986; 12: 245–73
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
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
Ullah MI, Newman GB, Saunders KB. Influence of age on response to ipratropium and salbutamol in man. Thorax 1981; 36: 523–9
Dauchot P, Gravenstein JS. Effects of atropine on the electrocardiogram in different age groups. Clin Pharmacol Ther 1971; 12: 274–80
Kelliher GJ, Conahan ST. Changes in vagal activity and response to muscarinic receptor agonists with age. J Gerontol 1980; 45: 842–9
Shepherd AMM, Elfellah HS. Effect of age on muscarinic responses in the rat heart [abstract]. Clin Res 1984; 32: 862A
Fink RI, Kilternan DG, Griffin J, et al. Mechanism of insulin resistance in ageing. J Clin Invest 1983; 50: 1523–35
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
Oba K, Nakano H, Okazaki K. Mild glucose intolerance in the elderly. Nippon Rinsho 1996; 54: 2773–8
Meneilly GS, Dawson K, Tessier D. Alterations in glucose metabolism in the elderly patient with diabetes. Diabetes Care 1993; 16: 1241–8
Marker JC, Cryer PE, Clutter WE. Attenuated glucose recovery from hypoglycemia in the elderly. Diabetes 1992; 41: 671–8
Brodows RG. Benefits and risks with glyburide and glipizide in elderly NIDDM patients. Diabetes Care 1992; 15: 75–80
Jennings PE. Oral antihyperglycaemics: considerations in older patients with non insulin dependent diabetes mellitus. Drugs Aging 1997; 10: 323–31
Irvine NA, Shepherd AMM. Age and blood pressure determine vasodepressor response to sodium nitroprusside. J Cardiovasc Pharmacol 1984; 6: 816–21
Shammas E, Dickstein K. Drug selection for optimal treatment of hypertension in the elderly. Drugs Aging 1997; 11: 19–26
Verhaeverbeeke I, Mets T. Drug induced orthostatic hypotension in the elderly. Drug Saf 1997; 17: 105–18
Schwartz JB. Calcium antagonist in the elderly. Drugs Aging 1996; 9: 24–36
Shepherd AMM, Hewick DS, Moreland TA, et al. Age as a determinant of sensitivity to warfarin. Br J Pharmacol 1977; 4: 315–20
Routledge PA, Chapman PH, Davies DM, et al. Factors affecting warfarin requirements. Eur J Clin Pharmacol 1979; 15: 319–22
Jones BR, Baran A, Reidenberg MM. Evaluating patients’ warfarin requirements. J Am Geriatr Soc 1980; 28: 10–12
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
Feely J, Coakly D. Altered pharmacodynamics in the elderly. Clin Geriatr Med 1990; 6: 269–83
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
Kimmick GG, Fleming R, Muss HB, et al. Cancer chemotherapy in older adults: a tolerability study. Drugs Aging 1997; 10: 34–49
Horner TD, Stanski DR. The effect of increasing age on thiopental disposition and anesthesia requirements. Anesthesiology 1985; 62: 714–24
Avram M, Sanghui R, Henthorn TK, et al. Determinants of thiopental induction dose requirements. Anesth Analg 1993; 76: 10–17
Jones AG, Hunter JM. Anaesthesia in the elderly, special considerations. Drugs Aging 1996; 9: 319–31
Hetzel W. Antikonvulsive Behandlung im höheren Lebensalter — Grundlagen und Differentialindikation. Fortschr Neurol Psychiatr 1997; 65: 261–77
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
Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil, model application. Anesthesiology 1997; 86: 24–33
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
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
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
Morrison RL, Katz IR. Drug-related cognitive impairment: current progress and recurrent problems. Annu Rev Gerontol Geriatr 1989; 9: 232–84
Ried LD, Johnson RE, Gettman OA. Benzodiazepine exposure and functional status in older people. J Am Geriatr Soc 1998; 46: 71–6
Castleden CM, George CF, Marcer D, et al. Increased sensitivity to nitrazepam in old age. BMJ 1977; 1: 10–2
Bressler R. Adverse drug reactions. In: Bressler R, Katz MD, editors. Geriatric Pharmacology. New York: McGraw-Hill, 1993: 41–61
Oxman TE. Antidepressants and cognitive impairment in the elderly. J Clin Psychiatry 1996; 57Suppl. 5: 38–44
Zaleon CR, Guthrie SK. Antipsychotic drug use in older adults. Am J Hosp Pharm 1994; 51: 2917–43
Livingstone RL, Zucker DK, Isenberg K, et al. Tricyclic antidepressants and delirium. J Clin Psychiatry 1983; 44: 173–6
Newhouse P. Use of serotonin selective reuptake inhibitors in geriatric depression. J Clin Psychiatry 1996; 57Suppl. 5: 12–22
Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging 1993; 3: 335–48
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
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
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
Cumming RG. Epidemiology of medication-related falls and fractures in the elderly. Drugs Aging 1998: 12: 43–53
Mattson RH. Antiepileptic drug monitoring: a reappraisal. Epilepsia 1995; 36Suppl. 5: S22–9
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
Lynch RA, Horowitz LN. Managing geriatric arrhythmias: II. Drug selection and use. Geriatrics 1991; 46: 41–4
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
Schulz M, Schmoldt A. Zusammenstellung therapeutischer und toxischer Plasmakonzentrationen von Arzneistoffen. Anaesthesist 1994; 43: 835–44
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
Reynolds DJM, Aronson JK. ABC of monitoring drug therapy: making the most of plasma drug concentration measurements. BMJ 1993; 306: 48–51
Spector R, Park GD, Johnson GF, et al. Therapeutic drug monitoring. Clin Pharmacol Ther 1988; 43: 345–53
Tonkin AL, Bochner F. Therapeutic drug monitoring and patient outcome: a review of the issues. Clin Pharmacokinet 1994; 27: 169–74
Campbell M. Community-based therapeutic drug monitoring: useful development or unnecessary distraction? Clin Pharmacokinet 1995; 28: 271–4
von Harnack G-A, Janssen F. Pädiatrische Dosistabellen. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1989
Willmore LJ. The effect of age on the pharmacokinetics of anti-epileptic drugs. Epilepsia 1995; 36Suppl. 5: S14–S21
Lewis DA, Reeves DS. Antibiotics at the extremes of age: choices and constraints. J Antimicrob Chemother 1994; 34Suppl. A: 11–8
Bonetti A, Franceschi T, Apostoli P, et al. Cisplatin pharmacokinetics in elderly patients. Ther Drug Monit 1994; 16: 477–82
Dahl SG. Plasma level monitoring of antipsychotic drugs: clinical utility. Clin Pharmacokinet 1986; 11: 36–61
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
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
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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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DOI: https://doi.org/10.2165/00002512-199813050-00003