Therapeutic drug monitoring in the elderly

American Journal of Therapeutics

Volumn 3, Issue 12, 1996, Pages 839-860

  Ruiz, Jorge G ^a   Array, Samir ^b   Lowenthal, David T ^b  

^a Mountain Home Veterans Affairs Medical Center   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

geropharmacology; pharmacodynamics; pharmacokinetics; therapeutic drug monitoring

Indexed keywords

AMIKACIN; DIGOXIN; GENTAMICIN; PHENYTOIN; THEOPHYLLINE; TOBRAMYCIN;

DIGOXIN BLOOD LEVEL; DOSE KIDNEY FUNCTION RELATION; DRUG ABSORPTION; DRUG CLEARANCE; DRUG HALF LIFE; DRUG MONITORING; ELDERLY CARE; GLOMERULUS FILTRATION RATE; HUMAN; PRIORITY JOURNAL; REVIEW; THEOPHYLLINE BLOOD LEVEL;

EID: 0030427448     PISSN: 10752765     EISSN: None     Source Type: Journal    
DOI: 10.1097/00045391-199612000-00008     Document Type: Review

References (213)

1. Health Care Financing Administration, Office of National Cost Estimates: National Health Expenditures, 1988. Health Care Financing Rev 1990;11:1-41.
2. Chrischilles EA, Foley DJ, Wallace RB, et al: Use of medication by persons 65 and over: Data from the established populations for epidemiologic studies of the elderly. J Gerontol 1992;47:M137-144.
3. Williamson J, Chopin JM: Adverse reactions to prescribed drugs in the elderly: a multicentre investigation. Age Ageing 1980;9:73-80.
4. Miller RR: Drug surveillance utilizing epidemiologic methods: A report from the Boston Collaborative Drug Surveillance Program. Am J Hosp Pharm 1973;30:584-592.
5. Spector R, Park GD, Johnson GF, Vesell ES: Therapeutic drug monitoring. Clin Pharmacol Ther 1988;43:345-353.
6. Reynolds DJM, Aronson JK: ABC of monitoring drug therapy. Making the most of plasma drug concentration measurements. BMJ 1993;306:48-51.
7. Sacher RA, McPherson RA: Widmanns's Clinical Interpretation of Laboratory Tests. FA Davis Company, Philadelphia, 1991.
8. Annesley TM: Special considerations for geriatric therapeutic drug monitoring. Clin Chem 1989;35:1337-1341.
9. Rock RC: Monitoring therapeutic drug levels in older patients. Geriatrics 1985;40:75-86.
10. Mitenko PA: Drug monitoring in the elderly. Clin Biochem 1986;19:145-149.
11. Koch-Weser J: Serum drug concentrations as therapeutic guides. N Engl J Med 1972;287:227-231.
12. Koch-Weser J: Serum drug concentrations in clinical perspective. Ther Drug Monitor 1981;3:3-16.
13. Ariens EJ: Drug levels in the target tissues and effect. Clin Pharmacol Ther 1974;16:155-175.
14. Shepherd AMM: Physiological changes with aging. Relevance to study design. In: Drug Studies in the Elderly (Eds. Cutler N, Narang P), Plenum Medical Book Company, New York, 1986, pp. 49-67.
15. Greenblatt DJ, Koch-Weser J: Clinical pharmacokinetics II. N Engl J Med 1975;293:964-970.
16. Swift CG, Triggs EJ: Clinical pharmacokinetics in the elderly. In: Swift CG (Eds). Clinical Pharmacology in the Elderly (Ed. Swift CG), Marcel Dekker, New York, 1987, pp. 31-82.
17. Bender AD: Effect of age on intestinal absorption: Implications for drug absorption in the elderly. J Am Geriatr Soc 1968;16:1331-1339.
18. Geokas MC, Haverback BJ: The aging gastrointestinal tract. Am J Surg 1969;117:881-892.
19. Kekki M, Samloff IM, Ihamaki T, Varis T, Siurala M: Age and sex-related behaviour of gastric acid secretion at the population level. Scand J Gastroenterol 1982;17:737-743.
20. Shargel L, Yu ABC: Applied Biopharmaceutics and Pharmacokinetics. Appleton & Lange, East Norwalk, 1993.
21. Dvorchik BH, Vesell ES: Pharmacokinetic interpretation of data gathered during therapeutic drug monitoring. Clin Chem 1976;22:868-878.
22. Greenblatt DJ, Koch-Weser J: Clinical pharmacokinetics I. N Engl J Med 1975;293:702-705.
23. Rowland M: Plasma protein binding and therapeutic drug monitoring. Ther Drug Monitor 1980;2:29-37.
24. Levy RH, Moreland TA: Rationale for monitoring free drug levels. Clin Pharmacokinet 1984;9:1-9.
25. Shock NW, Watkin DM, Yiengst BS, Norris AH, Gaffney GW, Gregerman RI, Falzone JA: Age differences in water content of the body as related to basal oxygen consumption in males. J Gerontol 1963;18:1-8.
26. Forbes GB, Reina JC: Adult lean body mass declines with age: Some longitudinal observations. Metabolism 1970;19:653-663.
27. Adelman LS, Liebman J: Anatomy of body water and electrolytes. Am J Med 1959;27:256-277.
28. Greenblatt DJ, Sellers EM, Shader RI: Drug disposition in old age. N Engl J Med 1982;306:1081-1088.
29. Ewy GA, Kapadia GG, Yao L, Lullin M, Marcus FI: Digoxin metabolism in the elderly. Circulation 1969;39: 449-453.
30. Nation RL, Triggs EJ: Lignocaine kinetics in cardiac patients and aged subjects. Br J Clin Pharmacol 1977;4: 439-148.
31. Cusack B, Kelly JG, Lavan J, Noel J, O'Malley K: Pharmacokinetics of lignocaine in the elderly. Br J Clin Pharmacol 1980;9:293-294.
32. Chan S, Gerson B: Free Drug Monitoring. Clin Lab Med 1987;7:279-287.
33. Greenblatt DJ, Sellers EM, Koch-Weser J: Importance of protein binding for the interpretation of serum or plasma drug concentrations. J Clin Pharmacol 1982;22: 259-263.
34. Schmucker DL: Aging and drug disposition: an update. Pharmacol Rev 1985;37:133-148.
35. Baird-Lambert J, Manglick MP, Wall M, Buchanan N: Identifying patients who might benefit from free phenytoin monitoring. Ther Drug Monitor 1987;9:134-138.
36. Piafsky KM: Disease induced changes in the plasma binding of basic drugs. Clin Pharmacokinet 1980;5:246-262.
37. Paxton JW: Alpha-1 acid glycoprotein and binding of basic drugs. Methods Find Exp Clin Pharmacol 1983;5: 635-648.
38. Paxton JW, Briant RH: Alpha-1 acid glycoprotein concentrations and propranolol binding in elderly patients with acute illness. Br J Clin Pharmacol 1984;18:806-810.
39. Friedman H, Greenblatt DJ: Rational therapeutic drug monitoring. JAMA 1986;256:2227-2233.
40. Verbeeck RK, Cardinal J, Wallace SM: Effect of age and sex on the plasma binding of acidic and basic drugs. Eur J Clin Pharmacol 1984;27:91-97.
41. Greenblatt DJ, Abernethy DR, Shader RI: Pharmacokinetic aspects of drug therapy in the elderly. Ther Drug Monitor 1986;8:249-255.
42. Yuen GJ: Altered Pharmacokinetics in the elderly. Clin Geriatr Med 1990;6:257-267.
43. Godin DV: Pharmacokinetics: disposition and metabolism of drugs. In: Principles of Pharmacology: Basic Concepts and Clinical Applications (Eds. Munson PL, Mueller RA, Breese GR), Chapman & Hall, New York, 1995, pp. 39-74.
44. Bender AD: The effect of increasing age on the distribution of peripheral blood flow in man. J Am Geriatr Soc 1965;13:192-198.
45. Bach B, Hansen JM, Kampmann JP, N RS, Skovsted L: Disposition of antipyrine and phenytoin correlated with age and liver volume in men. Clin Pharmacokinet 1981;6:389-396.
46. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OFW: The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1989;9:297-301.
47. Schmucker DL, Woodhouse KW, Wang RK, Wynne H, James OF, McManus M, Kremers P: Effects of age and gender on in vitro properties of human liver microsomal monooxygenases. Clin Pharmacol Ther 1990;48: 365-374.
48. Turner N, Scarpace PJ, Lowenthal DT: Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 1992;32:271-302.
49. Ruiz JG, Lowenthal DT: Geriatric pharmacology. In: Principles of Pharmacology. Basic Concepts and Clinical Applications (Eds. Munson PL, Mueller RA, Breese GR), Chapman & Hall, New York, 1995, 1717-1726.
50. Wynne HA, Mutch E, James OFW, Wright P, Rawlins MD, Woodhouse KW: The effect of age upon the affinity of microsomal microoxygenase enzymes for substrate in human liver. Age Ageing 1988;17:401-405.
51. Waser PG: The cholinergic receptor. J Pharm Pharmacol 1960;12:577-594.
52. Cusson J, Nattel S, Mathews RT, Talajic M, Lawand S: Age-dependent lidocaine disposition in patients with acute myocardial infarction. Clin Pharmacol Ther 1985; 37:381-386.
53. Abernethy DR, Greenblatt DJ: Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol 1983;5:1093-1096.
54. Cusack B, Kelly JG, Lavan J, Noel J, O'Malley K: Theophylline kinetics in relation to age: the importance of smoking. Br J Clin Pharmac 1980;10:109-114.
55. Antal EJ, Kramer PA, Mercik SA, Chapron DJ, Lawson IR: Theophylline pharmacokinetics in advanced age. Br J Clin Pharmac 1981;12:637-645.
56. Au WYW, Dutt AK, De Souza N: Theophylline kinetics in chronic obstructive airway disease in the elderly. Clin Pharmacol Ther 1985;37:472-478.
57. Richer M, Lam F: Hypoxia, Arterial pH and theophylline disposition. Clin Pharmacokinet 1993;25:283-299.
58. Schenker S, Bay M: Drug disposition and hepatotoxicity in the elderly. J Clin Gastroenterol 1994;18:232-237.
59. Davis DF, Shock NW: Age changes in glomerular filtration rates, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest 1950;29: 496-507.
60. Rowe JW, Andres R, Tobin JD, Norris AH, Shock NW: The effect of age on creatinine clearance in men: A cross-sectional and longitudinal study. J Gerontol 1976; 31:155-163.
61. Watkin DM, Shock NW: Agewise standard value for Cin, Cpah and Tmpah in adult males. J Clin Invest [Abstract] 1955;34:965.
62. Reidenberg MM, Camacho M, Kluger BA, Drayer DE: Aging and renal clearance of procainamide and acetylprocainamide. Clin Pharmacol Ther 1980;28:732-735.
63. Bauer L, Blouin R: Gentamicin pharmacokinetics: Effect of aging in patients with normal renal function. J Am Geriatr Soc 1982;30:309-311.
64. Bauer LA, Blouin RA: Influence of age on tobramycin pharmacokinetics in patients with normal renal function. Antimicrob Agents Chemother 1981;20:587-589.
65. Zaske DE, Irvine P, Strand LM, Strate RG, Cipolle RJ, Rotschafer J: Wide interpatient variations in gentamicin dose requirements for geriatric patients. JAMA 1982;248: 3122-3126.
66. Tsang P, Gerson B: Understanding digoxin use in the elderly patient. Clin Lab Med 1990;10:479-492.
67. Passmore AP, Johnston GD: Digoxin toxicity in the aged. Characteristics and avoiding the problem. Drugs Aging 1991;1:364-379.
68. Falch D: The influence of kidney function, body size and age on plasma concentration and urinary excretion of digoxin. Acta Med Scand 1973;194:251-256.
69. Cusack B, Kelly J, O'Malley K, Noel J, Lavan J, Morgan J: Digoxin in the elderly: Pharmacokinetic consequences of old age. Clin Pharmacol Ther 1979;25:772-776.
70. Mooradian AD, Wynn EM: Pharmacokinetic prediction of serum digoxin concentration in the elderly. Arch Intern Med 1987;147:650-653.
71. Koren G, Soldin SJ: Cardiac glycosides. Clin Lab Med 1987;7:587-606.
72. Aronson JK, Hardman M: ABC of monitoring drug therapy: digoxin. BMJ 1992;305:1149-1152.
73. Kelly RA, Smith TW: Use and misuse of digitalis blood levels. Heart Dis Stroke 1992;1:117-122.
74. McCormack JP, Jewesson PJ: A critical reevaluation of the "therapeutic range" of aminoglycosides. Clin Infect Dis 1992;14:320-339.
75. Lakatta EG: Age related alterations in the cardiovascular response to adrenergic-mediates stress. Fed Proc 1980;39:3173-3177.
76. Scarpace P: Decreased receptor activation with age. Can it be explained by desensitization? J Am Geriatr Soc 1988;36:1067-1071.
77. +-ATPase and age-dependent digitalis toxicity. Pharmacologist [Abstract] 1977;19:132.
78. Bolinder J, Ostman J, Arner P: Influence of aging on insulin receptor binding and metabolic effects of insulin on human adipose tissue. Diabetes 1983;32:959-964.
79. Pagano G, Cassader M, Diana A, Pisu E, Bozzo C, Ferrero F, Lenti G: Insulin resistance in the aged: The role of peripheral insulin receptors. Metabolism 1981;30: 46-49.
80. Friedman H, Ochs HR, Greenblatt DJ: Tissue distribution of diazepam and its metabolite desmethyldiazepam: A human autopsy study. J Clin Pharmacol 1985; 25:613-615.
81. Krakauer R, Steiness E: Digoxin concentration in choroid plexus, brain, and myocardium in old age. Clin Pharmacol Ther 1978;24:454-158.
82. Hoffman BF, Bigger JT: Digitalis and allied cardiac glycosides. In: Goodman and Gilman's The Pharmacologic Basis of Therapeutics (Eds. Gilman A, Goodman L, Rall T), MacMillan, New York, 1985, pp. 716-747.
83. Swift CG: Pharmacodynamics: Changes in homeostatic mechanisms, receptor and target organ sensitivity in the elderly. Br Med Bull 1990;46:36-52.
84. Jackson SHD: Pharmacodynamics in the elderly. J R Soc Med 1994;23:5-7.
85. Lamy PP: Physiological changes due to age. Pharmacodynamic changes of drug action and implications for therapy. Drugs Aging 1991;1:385-404.
86. Robertson DRC, Waller DG, Renwick AG, George CF: Age related changes in the pharmacokinetics and pharmacodynamics of nifedipine. Br J Clin Pharmacol 1988; 25:297-305.
87. Ajayi AA, Hockings N, Reid JL: Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol 1986;21: 349-359.
88. Caird FI, Andrews GR, Kennedy RD: Effect of posture on blood pressure in the elderly. Br Heart J 1973;35:527-530.
89. Shepherd AMM, Hewick DS, Moreland TA, Stevenson IH: Age as a determinant of sensitivity to warfarin. Br J Clin Pharmacol 1977;4:315-320.
90. Schwinghammer TL, Antal EJ, Kubacka RT, Hackimer ME, Johnston JM: Pharmacokinetics and pharmacodynamics of glyburide in young and elderly nondiabetic adults. Clin Pharm 1991;10:532-538.
91. Castleden CM, George CF, Marcer D, Hallet C: Increased sensitivity to nitrazepam in old age. BMJ 1977;1:10-12.
92. Swift CG, Ewen JM, Clarke P: Responsiveness to oral diazepam in the elderly: Relationship to total and free plasma concentrations. Br J Clin Pharmacol 1985;20:119-128.
93. Hinrichs JV, Ghoneim MM: Diazepam, behaviour and ageing: increased sensitivity or lower baseline performance. Psychopharmacology 1987;92:100-105.
94. Stewart RB, Caranasos GJ: Medication compliance in the elderly. Med Clin North Am 1989;73:1551-1563.
95. Weintraub M: Compliance in the elderly. Clin Geriatr Med 1990;6:445-152.
96. Rudd P, Lenert L: Pharmacokinetics as an aid to optimizing compliance with medications. Clin Pharmacokinet 1995;28:1-6.
97. Urquhart J: Role of patient compliance in clinical pharmacokinetics. Clin Pharmacokinet 1994;27:202-215.
98. Cramer JA, Scheyer RD, Mattson RH: Compliance declines between clinic visits. Arch Intern Med 1990;150: 1509-1510.
99. Meredith PA, Elliot HL: Therapeutic coverage: reducing the risks of partial compliance. Br J Clin Pract Suppl 1994;73:13-17.
100. Caranasos GJ, Stewart RB, Cluff LE: Drug-related illness leading to hospitalization. JAMA 1974;228:713-717.
101. Lindley CM, Tully MP, Paramsothy V, Tallis RC: Inappropriate medication is a major cause of adverse drug reactions in elderly patients. Age Ageing 1992;21:294-300.
102. Grymonpre RE, Mitenko PA, Sitar DS, Aoki FY, Montgomery PR: Drug associated hospital admissions in older medical patients. J Am Geriatr Soc 1988;36:1092-1098.
103. Montamat SC, Cusack B: Overcoming problems with polypharmacy and drug misuse in the elderly. Clin Geriatr Med 1992;8:143-158.
104. Carbonin P, Paho M, Bernabe R, Spadari A: Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? J Am Geriatr Soc 1991;39: 1093-1099.
105. Gurwitz JH, Avorn J: The unambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991;114:956-966.
106. Nolan L, O'Malley K: Prescribing for the elderly. Part I: Sensitivity of the elderly to adverse drug reactions. J Am Geriatr Soc 1986;36:142-144.
107. Besdine RW: Introduction. In: Merck Manual of Geriatrics (Eds. Abrams WB, Berkow R, Fletcher AJ), Merck and Co, New Jersey, 1990, pp. 2-4.
108. Divoll MK, Greenblatt DJ: Drug interactions and adverse drug reactions in the elderly. In: Clinical Pharmacology in the Elderly (Ed. Swift C), Marcel Dekker Inc., New York, 1987, pp. 119-145.
109. Lamy PP: The elderly and drug interactions. J Am Geriatr Soc 1986;34:586-592.
110. Bussey HI: Update on the influence of quinidine and other agents on digitalis glycosides. Am Heart J 1984;107: 143-146.
111. Doering W: Quinidine-digoxin interaction. Pharmacokinetics, underlying mechanism and clinical implications. N Engl J Med 1979;301:400-404.
112. Mooradian AD: Digitalis. An update of clinical pharmacokinetics, therapeutic monitoring techniques and treatment recommendations. Clin Pharmacokinet 1988;15: 165-179.
113. Walker AM, Cody TRJ, Greenblatt DJ, Jick H: Drug toxicity in patient receiving digoxin and quinidine. Am Heart J 1983;105:1025-1028.
114. Travers EM: Misuse of therapeutic drug monitoring: An analysis of causes and methods for improvement. Clin Lab Med 1987;7:453-471.
115. Cannon DJ: Therapeutic drug monitoring revisited. Clin Chem 1991;37:141.
116. D'Angio RG, Stevenson JG, Lively BT, Morgan JE: Therapeutic drug monitoring: Improved performance through educational intervention. Ther Drug Monitor 1990;12:173-181.
117. Wilkinson DS: Establishing a therapeutic drug monitoring consultation service. Clin Lab Med 1987;7:473-484.
118. Elin RJ: Computer-assisted therapeutic drug monitoring. Clin Lab Med 1987;7:485-492.
119. Bachmann KA, Forney RB, Gronau G: Use of limited laboratory-acquired therapeutic drug monitoring data in determining individualized drug requirements. Ann Clin Lab Sci 1987;17:52-59.
120. Bachmann K, Pongsin V, Forney JR, Gronau G: Experience with a computer based technique for estimating pharmacokinetic constants from limited data. Ther Drug Monitor 1985;7:258-264.
121. Vozeh S, Hillman R, Wandell M, Ludden T, Sheiner L: Computer-assisted drug assay interpretation based on bayesian estimation of individual pharmacokinetics: Application to lidocaine. Ther Drug Monitor 1985;7: 66-73.
122. Jelliffe RW, Tahani B: Pharmacoinformatics: equations for serum drug assay error patterns; implications for therapeutic drug monitoring and dosage. Proc Annu Symp Comput Appl Med Care 1993;517-521.
123. Schumacher GE, Barr J: Bayesian and threshold probabilities in therapeutic drug monitoring: When can serum drug concentrations alter clinical decisions? Am J Hosp Pharm 1994;51:321-327.
124. Eraker SA, Sasse L: The serum digoxin test and digoxin toxicity: a bayesian approach to decision making. Circulation 1981;64:409-420.
125. El Desoky E, Meinshausen, Buhl K, Engel A, Harings-Kaim A, Drewelow B, Klotz U: Generation of pharmacokinetic data during routine therapeutic drug monitoring: Bayesian approach vs. pharmacokinetic studies. Ther Drug Monitor 1993;15:281-288.
126. Bottger H, Oellerich M, Sybrecht GW: Use of aminoglycosides in critically ill patients: individualization of dosage using Bayesian statistics and pharmacokinetic principles. Ther Drug Monitor 1988;10:280-286.
127. Levine M, Chang T: Therapeutic drug monitoring of Phenytoin. Rationale and current status. Clin Pharmacokinet 1990;19:341-358.
128. Aranow WS: Clinical use of digitalis. Comp Ther 1992;18:38-41.
129. Johnson BF, Bye CE, Jones GE, Sabey GA: The pharmacokinetics of beta-methyl digoxin compared with digoxin tablets and capsules. Eur J Pharmacol 1976;10:231-236.
130. Dobbs RJ, O'Neill JA, Desmukh AA, Nicholson PW, Dobbs SM: Serum concentration monitoring of cardiac glycosides. How helpful is it for adjusting dosage regimens? Clin Pharmacokinet 1991;20:175-193.
131. Nolan PE, Mooradian AD: Digoxin. In: Geriatric Pharmacology (Eds. Bressler R, Katz MD), McGraw Hill Inc, New York, 1993, pp. 151-163.
132. Aronson WS, Grahame-Smith DG, Wigley FM: Monitoring digoxin therapy. Q J Med 1978;186:111-122.
133. Gault MH, Longerich LL, Loo JC, Ko PT, Rine A, Vasdev SC, Dawe MA: Digoxin biotransformation. Clin Pharmacol Ther 1984;35:74-82.
134. Doherty JE, Perkins WA: Digoxin metabolism in hypoand hyperthyroidism: studies with tritriated digoxin in thyroid disease. Ann Intern Med 1966;64:489-507.
135. Smith TW, Haber E: Digitalis. N Engl J Med 1973;289: 1063-1072.
136. + uptake rate and responsiveness to digoxin in rat left atrial muscle. J Pharmacol Exp Ther 1989;248:104-110.
137. Katano Y, Kennedy RH, Stemmer PM, Temma K, Akera T: Aging and digitalis sensitivity of cardiac muscle in rats. Eur J Pharmacol 1985;113:167-178.
138. Kelly JG, Copeland S, McDevitt DG: Erythrocyte cation transport and age: effects of digoxin and furosemide. Clin Pharmacol Ther 1983;34:159-163.
139. Dimant J, Merrit W: Serum digoxin levels in elderly nursing home patients: Appraisal of routine periodic measurements. J Am Geriatr Soc 1978;26:328-379.
140. Joy ME, Higbee MD: Extracardiac manifestations of digitalis toxicity in the elderly. Hosp Formul 1985;20: 1015-1020.
141. Goldman EL, Van Gelder J, Holmes R, Hull AR, Sanford OP: Prospective comparative study of variable dosage and variable frequency regimens for administration of gentamicin. Antimicrob Agents Chemother 1975;8:434-438.
142. Goldstein RL, Stanton BA, Lipson MJ: Clinical utility of serum digoxin level tests in hospitalized elderly patients. Arch Phys Med Rehab 1986;67:34-37.
143. Portnoi VA: Digitalis delirium in elderly patients. J Clin Pharmacol 1979;19:747-750.
144. Smith TW, Haber E: Digoxin intoxication: the relationship of clinical presentation to serum digoxin concentration. J Clin Invest 1970;49:2377-2386.
145. Piergies AA, Worwag EM, Atkinson AJ: A concurrent audit of high digoxin plasma levels. Clin Pharmacol Ther 1994;55:353-358.
146. Beller GA, Smith TW, Abelmann WH, Haber E, Hood WB: Digitalis intoxication. A prospective clinical study with serum level concentrations. N Engl J Med 1971;18: 989-997.
147. Bloom JW, Barreuther AD: Drug therapy of airway obstructive diseases. In: Geriatric Pharmacology (Eds. Bressler R, Katz MD), McGraw Hill Inc, New York, 1993, pp. 507-533.
148. Bauer LA, Blouin RA: Influence of age on theophylline clearance in patients with chronic obstructive pulmonary disease. Clin Pharmacokinet 1981;6:469-174.
149. Fox RW, Samaan S, Bukantz SC, Lockey RF: Theophylline kinetics in a geriatric group. Clin Pharmacol Ther 1983;34:60-67.
150. Jusko WJ, Koup JR, Vance JW, Schentag JJ, Kuritzky P: Intravenous theophylline therapy: Nomograms guidelines. Ann Intern Med 1977;86:400-404.
151. Talseth T, Boyer NP, Kongerud J, Bredesen JE: Aging, cigarette smoking and oral theophylline requirement. Eur J Clin Pharmacol 1981;21:33-37.
152. Jusko WJ: Role of tobacco smoking in pharmacokinetics. J Pharmacokinet Biopharmaceut 1978;6:7-39.
153. Hunt SN, Jusko WJ, Yurchak AM: Effect of smoking of theophylline disposition. Clin Pharmacol Ther 1976;19: 546-551.
154. Jonkman JHG: Therapeutic consequences of drug interactions with theophylline pharmacokinetics. J All Clin Immunol 1986,78:736-742.
155. Chandler MHH, Clifton GD, Burki NK, Hunt BA, Blouin RA: Pulmonary function in the elderly: Response to theophylline bronchodilation. J Clin Pharmacol 1990;30:330-335.
156. Banerjee DK, Lee GS, Malik SK, Daly S: Underdiagnosis of asthma in the elderly. Br J Dis Chest 1987;81:23-29.
157. Chrystyn H, Mulley BA, Peake MD: Dose response relation to oral theophylline in severe chronic obstructive airway disease. BMJ 1988;297:1506-1510.
158. Mitenko PA, Ogilvie RJ: Rational intravenous doses of theophylline. N Engl J Med 1973;289:600-603.
159. Pincus MR, Abraham NZ: Toxicology and therapeutic drug monitoring. In: Clinical Diagnosis and Management by Laboratory Methods (Eds. Nelson D, Tomar R, Washington J), WB Saunders Company, Philadelphia, 1991, pp. 363-384.
160. Vozeh S, Kewitz G, Perruchoud A, Tschan M, Kopp K, Heitz M, Follath F: Theophylline serum concentration and therapeutic effect in severe acute bronchial obstruction: the optimal use of intravenously administered aminophylline. Am Rev Respir Dis 1982;125:181-184.
161. Klein JJ, Lefkowitz MS, Spector S, Cherniack R: Relationship between serum theophylline levels and pulmonary function before and after inhaled beta-agonist in "stable" asthmatics. Am Rev Respir Dis 1983;127:413-416.
162. Holford N, Black P, Couch R, Kennedy J, Briant R: Theophylline target concentrations in severe airways obstruction - 10 or 20 mg/L. Clin Pharmacokinet 1993; 25:495-505.
163. Rogers RM, Owens GR, Pennock BE: The pendulum swings again. Toward a rational use of theophylline. Chest 1985;87:280-282.
164. Aronson JK, Hardman M, Reynolds DJM: ABC of monitoring drug therapy: theophylline. BMJ 1992;305: 1355-1358.
165. Jacobs MH, Senior RM, Kessler G: Clinical experience with theophylline: relationship between dosage, serum concentration and toxicity. JAMA 1976;235:1983-1986.
166. Paloucek FP, Rodvoid KA: Evaluation of theophylline overdoses and toxicities. Ann Emerg Med 1988;17:135-144.
167. Shannon M, Lovejoy F: The influence of age vs. peak serum concentration on life threatening events after chronic theophylline intoxication. Arch Intern Med 1990;150:2045-2048.
168. Singer EP: Seizures due to theophylline overdose. Chest 1985;87:755-757.
169. Yarnell PR, Chu NS: Focal seizures and aminophylline. Neurology 1975;25:819-822.
170. Nakada T, Kwee L, Lernere AM, Remler MP: Theophylline induced seizures: clinical and pathophysiologic aspects. West J Med 1983;136:371-374.
171. Levine JH, Michael JR, Guarnieri T: Multifocal atrial tachycardia: a toxic effect of theophylline. Lancet 1985;i: 12-14.
172. Dull AK, DeSoyza ND, Au WY, Hargis JL, Tuek RL: The effect of aminophylline on cardiac rhythm in advance chronic obstructive pulmonary disease: correlation with serum theophylline levels. Eur J Respir Dis 1983;64:264-270.
173. Jenne JW: Effect of disease states on theophylline elimination. J Allergy Clin Immunol 1986;78:727-735.
174. Ben-Yehuda A, Weksler ME: Host resistance and the immune system. Clin Geriatr Med 1992;8:701-711.
175. Bender BS: Sepsis. Clin Geriatr Med 1992;8:913-924.
176. Reeves DS: Therapeutic drug monitoring of aminoglycoside antibiotics. Infection 1980;8(Suppl 33):S313-S320.
177. Aronson JK, Reynolds DJM: ABC of monitoring drug therapy. Aminoglycoside antibiotics. BMJ 1992;305:1421-1424.
178. Mullins RE, Lampasona V, Conn RB: Monitoring aminoglycoside therapy. Clin Lab Med 1987;7:513-529.
179. Bauer LA, Blouin RA: Influence of age on amikacin pharmacokinetics in patients without renal disease. Comparison with gentamicin and tobramycin. Eur J Clin Pharmacol 1983;24:639-642.
180. Matzke GR, Jameson JJ, Halstenson CE: Gentamicin disposition in young and elderly patients with various degrees of renal function. J Clin Pharmacol 1987;27:216-220.
181. Kaloyanides GJ, Pastoriza-Munoz E: Aminoglycoside nephrotoxicity. Kidney Int 1980;18:571-582.
182. Moore RD, Smith CR, Lietman PS: Association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis 1984; 149:443-448.
183. Moore RD, Smith CR, Lietman PS: Association of aminoglycoside plasma levels with therapeutic outcome in gram negative pneumonia. Am J Med 1984;77: 657-662.
184. Pechere JC, Dugal R: Clinical pharmacokinetics of aminoglycoside antibiotics. Clin Pharmacokinet 1979;4: 170-199.
185. Line DH, Poole GW, Waterworth PM: Serum streptomycin levels and dizziness. Tubercle Lond 1970;51:76-81.
186. Mawer GE, Ahmad R, Dobbs SM, McGough JG: Prescribing aids for gentamicin. Br J Clin Pharmac 1974;1:45-50.
187. Dahlgren JG, Anderson ET, Hewitt WL: Gentamicin blood levels a guide to nephrotoxicity. Antimicrob Agents Chemother 1975;8:58-62.
188. Wilson SE: Aminoglycosides: assessing the potential for nephrotoxicity. Surg Gynecol Obstet 1990;171 (Suppl): 24-30.
189. Meyer RD: Risk factors and comparison of clinical nephrotoxicity of aminoglycosides. Am J Med 1986; 80(Suppl 6B):119-125.
190. Moore RD, Smith CR, Lipsky JJ, Mellits ED, Lietman PS: Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med 1984;100:352-357.
191. Slaughter RL: Probability assessment approach to therapeutic drug monitoring: tobramycin. DICP 1989;23:240-244.
192. Hauser WA, Kurland LT: The epidemiology of epilepsy in Rochester Minnesota 1935 through 1967. Epilepsia 1975;16:1-66.
193. Luhdorf K, Jensen LK, Plesner AM: Etiology of seizures in the elderly. Epilepsia 1986;27:458-463.
194. Miller JW, Ferrendelli JA: Seizures and epilepsy. In: Principles of Geriatric Medicine and Gerontology (Eds. Hazzard WBEL, Blass JP, Ettinger WH, Halter JB), McGraw Hill Inc, New York, 1994, pp. 1089-1093.
195. Lloyd GK, Gillenwater G: Epilepsy and antiepileptic drugs. In: Principles of Pharmacology. Basic Concepts and Clinical Applications (Eds. Munson P, Mueller R, Breese G), Chapman & Hall, New York, 1995, 363-398.
196. Richens AA: Clinical pharmacokinetics of phenytoin. Clin Pharmacokinet 1979;4:153-169.
197. Hayes MJ, Langfman MJS, Short AH: Changes in drug metabolism with increasing age: 2. Phenytoin clearance and protein binding. Br J Clin Pharmac 1975;2:73-79.
198. Lambie DC, Caird FI: Phenytoin dosage in the elderly. Age Ageing 1977;6:133-137.
199. Bauer LA, Blouin RA: Age and phenytoin kinetics in adult epileptics. Clin Pharmacol Ther 1982;31:301-304.
200. Aronson JK, Hardman M, Reynolds DJ: ABC of monitoring drug therapy: phenytoin. BMJ 1992;305:1215-1218.
201. Kitani K, Masuda Y, Sato Y, Ohta M, Nokubo M: Increased anticonvulsant effect of phenytoin in aging BDF mice. J Pharmacol Exp Ther 1984;229:231-236.
202. Theodore WH: Antiepileptic drugs in the elderly. In: Drug Studies in the Elderly: Methodological concerns (Eds. Cutler N, Narang P), Plenum Medical Book Company, New York, 1986, pp. 273-282.
203. Reynold EH, Trimble MR: Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-581.
204. Reynolds EH, Chadwick D, Galbraith AW: One drug (phenytoin) in the treatment of epilepsy. Lancet 1976;1: 923-926.
205. Lambie DG, Johnson RH, Nanda RN, Shakir RA: Therapeutic and pharmacokinetic effects of increasing phenytoin in chronic epileptics on multiple drug therapy. Lancet 1976;ii:386-389.
206. Feldman RG, Pippenger CE: The relation of anticonvulsant drug levels to complete seizure control. J Clin Pharmacol 1976;16:51-59.
207. Troupin AS: The measurement of anticonvulsant agent levels. Ann Intern Med 1984;100:854-858.
208. Cobos JE: High-dose phenytoin in the treatment of refractory epilepsy. Epilepsia 1987;28:111-114.
209. Woo E, Chan YM, Yu YL, Chan YW, Huang CY: If a well-stabilized epileptic patient has a subtherapeutic antiepileptic drug levels, should the dose be increased? A randomized prospective study. Epilepsia 1988;29:129-139.
210. Mooradian AD, Hernandez L, Tamai IC, Marshall C: Variability of serum phenytoin concentrations in nursing home patients. Arch Intern Med 1989;149:890-892.
211. Troupin AS, Ojenmann LM: Paradoxical intoxication - a complication of anticonvulsant administration. Epilepsia 1975;16:753-758.
212. Patterson M, Heazelwood R, Smithurst B, Eadie MJ: Plasma protein binding of phenytoin in the aged: in vivo studies. Br J Clin Pharmacol 1982;13:423-425.
213. Leppik IE: Metabolism of antiepileptic medication: newborn to elderly. Epilepsia 1992;33(Suppl 4):S32-40.