Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-08T00:26:39.612Z Has data issue: false hasContentIssue false
  • English
  • Français

Individualization of drug therapy in older people

Published online by Cambridge University Press:  20 March 2014

P Scibona ,
F Angriman ,
C Vazquez ,
BL Ferreyro ,
AG Perelsztein ,
VA Simonovich ,
JR Jauregui ,
CG Musso  and
WH Belloso
P Scibona
Affiliation:
Clinical Pharmacology Section, Internal Medicine Service, University of Buenos Aires School of Medicine, Argentina
F Angriman
Affiliation:
Clinical Pharmacology Section, Internal Medicine Service, University of Buenos Aires School of Medicine, Argentina Department of Pharmacology, University of Buenos Aires School of Medicine, Argentina
C Vazquez
Affiliation:
Clinical Pharmacology Section, Internal Medicine Service, University of Buenos Aires School of Medicine, Argentina
BL Ferreyro
Affiliation:
Clinical Pharmacology Section, Internal Medicine Service, University of Buenos Aires School of Medicine, Argentina Department of Pharmacology, University of Buenos Aires School of Medicine, Argentina
AG Perelsztein
Affiliation:
Department of Pharmacology, University of Buenos Aires School of Medicine, Argentina
VA Simonovich
Affiliation:
Clinical Pharmacology Section, Internal Medicine Service, University of Buenos Aires School of Medicine, Argentina
JR Jauregui
Affiliation:
Ageing Biology Unit, Hospital Italiano de Buenos Aires, University of Buenos Aires School of Medicine, Argentina
CG Musso
Affiliation:
Ageing Biology Unit, Hospital Italiano de Buenos Aires, University of Buenos Aires School of Medicine, Argentina
WH Belloso*
Affiliation:
Clinical Pharmacology Section, Internal Medicine Service, University of Buenos Aires School of Medicine, Argentina Department of Pharmacology, University of Buenos Aires School of Medicine, Argentina
*
Address for correspondence: Dr Waldo Horacio Belloso, Clinical Pharmacology Section, Internal Medicine Service, Hospital Italiano de Buenos Aires, Juan D. Perón 4190 (C1181ACH), Buenos Aires, Argentina Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Older people are high consumers of prescription drugs and are at increasing risk of polypharmacy and adverse reactions. Pharmacokinetic and pharmacodynamic modifications due to age and co-morbidities are an important consideration, but pharmacological background evidence to guide safe and effective therapeutic approaches are often inadequate since the older population is under-represented in clinical trials. We review the pharmacokinetic and pharmacodynamic changes that are characteristic in old age and consider evidence regarding potentially safer prescription and monitoring of drugs commonly used in older patients. We also introduce the possible role of pharmacogenomics and therapeutic drug monitoring as tools to guide the individualization of drug therapy.

Keywords

agedpharmacokineticsdrug toxicitytherapeuticsdrug monitoringpharmacogenomics
Type
Review Article
Information
Reviews in Clinical Gerontology , Volume 24 , Issue 2 , May 2014 , pp. 145 - 157
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Wooten, JM. Pharmacotherapy considerations in elderly adults. South Med J 2012; 105: 437–45.CrossRefGoogle ScholarPubMed
2Lubitz, J, Cai, L, Kramarow, E, Lentzner, H. Health, life expectancy, and health care spending among the elderly. N Engl J Med 2003; 349: 1048–55.CrossRefGoogle ScholarPubMed
3McLean, AJ, Le Couteur, DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev 2004; 56: 163–84.CrossRefGoogle ScholarPubMed
4Aymanns, C, Keller, F, Maus, S, Hartmann, B, Czock, D. Review on pharmacokinetics and pharmacodynamics and the aging kidney. Clin J Am Soc Nephrol 2010; 5: 314–27.CrossRefGoogle ScholarPubMed
5Fulop, T Jr, Worum, I, Csongor, J, Foris, G, Leovey, A. Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects. Gerontology 1985; 31: 6–14.Google ScholarPubMed
6Ginsberg, G, Hattis, D, Russ, A, Sonawane, B. Pharmacokinetic and pharmacodynamic factors that can affect sensitivity to neurotoxic sequelae in elderly individuals. Environ Health Perspect 2005; 113: 1243–49.CrossRefGoogle ScholarPubMed
7Mangoni, AA, Jackson, SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2004; 57: 6–14.CrossRefGoogle ScholarPubMed
8Hutchinson, LC. OBC. Changes in pharmacokinetics and pharmacodynamics in the elderly patient. J Pharm Prac 2007; 20: 4–12.CrossRefGoogle Scholar
9Zoli, M, Magalotti, D, Bianchi, G, Gueli, C, Orlandini, C, Grimaldi, Met al.Total and functional hepatic blood flow decrease in parallel with ageing. Age Ageing 1999; 28: 29–33.CrossRefGoogle ScholarPubMed
10Young, LL, Lyon, CE. Effect of postchill aging and sodium tripolyphosphate on moisture binding properties, color, and Warner-Bratzler shear values of chicken breast meat. Poult Sci 1997; 76: 1587–90.CrossRefGoogle ScholarPubMed
11Esposito, C, Plati, A, Mazzullo, T, Fasoli, G, De Mauri, A, Grosjean, Fet al.Renal function and functional reserve in healthy elderly individuals. J Nephrol 2007; 20: 617–25.Google ScholarPubMed
12Lindeman, RD, Tobin, J, Shock, NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33: 278–85.CrossRefGoogle ScholarPubMed
13Coresh, J, Astor, B. Decreased kidney function in the elderly: clinical and preclinical, neither benign. Ann Intern Med 2006; 145: 299–301.CrossRefGoogle ScholarPubMed
14Wetzels, JF, Kiemeney, LA, Swinkels, DW, Willems, HL, den Heijer, M. Age- and gender-specific reference values of estimated GFR in Caucasians: the Nijmegen Biomedical Study. Kidney Int 2007; 72: 632–37.CrossRefGoogle ScholarPubMed
15Musso, CG, Macias Nunez, JF, Oreopoulos, DG. Physiological similarities and differences between renal aging and chronic renal disease. J Nephrol 2007; 20: 586–87.Google ScholarPubMed
16Perucca, E. Age-related changes in pharmacokinetics: predictability and assessment methods. Int Rev Neurobiol 2007; 81: 183–99.CrossRefGoogle ScholarPubMed
17Noreddin, AM, Haynes, V. Use of pharmacodynamic principles to optimise dosage regimens for antibacterial agents in the elderly. Drugs Aging 2007; 24: 275–92.CrossRefGoogle ScholarPubMed
18Butler, JM, Begg, EJ. Free drug metabolic clearance in elderly people. Clin Pharmacokinet 2008; 47: 297–321.CrossRefGoogle ScholarPubMed
19Mallet, L, Spinewine, A, Huang, A. The challenge of managing drug interactions in elderly people. Lancet 2007; 370: 185–91.CrossRefGoogle ScholarPubMed
20Wang, L. Changes in pharmacokinetics in the elderly and therapeutic drug monitoring of antiarrhythmic drugs. Life Sci J 2007; 4: 1–7.Google Scholar
21Merle, L, Laroche, ML, Dantoine, T, Charmes, JP. Predicting and preventing adverse drug reactions in the very old. Drugs Aging 2005; 22: 375–92.CrossRefGoogle ScholarPubMed
22Field, TS, Gurwitz, JH, Harrold, LR, Rothschild, J, DeBellis, KR, Seger, ACet al.Risk factors for adverse drug events among older adults in the ambulatory setting. J Am Geriatr Soc 2004; 52: 1349–54.CrossRefGoogle ScholarPubMed
23Delafuente, JC. Pharmacokinetic and pharmacodynamic alterations in the geriatric patient. Consult Pharm 2008; 23: 324–34.CrossRefGoogle ScholarPubMed
24Waltman, KWS (ed). Preventing Adverse Drug Reactions. Philadelphia: Hanley & Belfus; 2000.Google Scholar
25Catterson, ML, Preskorn, SH, Martin, RL. Pharmacodynamic and pharmacokinetic considerations in geriatric psychopharmacology. Psychiatr Clin North Am 1997; 20: 205–18.CrossRefGoogle ScholarPubMed
26El Desoky, ES. Pharmacokinetic-pharmacodynamic crisis in the elderly. Am J Ther 2007; 14: 488–98.CrossRefGoogle ScholarPubMed
27Abernethy, DR. Aging effects on drug disposition and effect. Geriatr Nephrol Urol 1999; 9: 15–19.CrossRefGoogle ScholarPubMed
28Hajjar, ER, Cafiero, AC, Hanlon, JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother 2007; 5: 345–51.CrossRefGoogle ScholarPubMed
29Weiss, BD, Lee, JK. Aging: is your patient taking too many pills? J Fam Pract 2012; 61: 652–61.Google ScholarPubMed
30Bressler, R, Bahl, JJ. Principles of drug therapy for the elderly patient. Mayo Clin Proc 2003; 78: 1564–77.CrossRefGoogle ScholarPubMed
31Willlams, CM. Using medications appropriately in older adults. Am Fam Physician 2002; 66: 1917–24.Google ScholarPubMed
32Topinkova, E, Baeyens, JP, Michel, JP, Lang, PO. Evidence-based strategies for the optimization of pharmacotherapy in older people. Drugs Aging 2012; 29: 477–94.CrossRefGoogle ScholarPubMed
33Marcum, ZA, Handler, SM, Boyce, R, Gellad, W, Hanlon, JT. Medication misadventures in the elderly: a year in review. Am J Geriatr Pharmacother 2010; 8: 77–83.CrossRefGoogle ScholarPubMed
34Gokula, M, Holmes, HM. Tools to reduce polypharmacy. Clin Geriatr Med 2012; 28: 323–41.CrossRefGoogle ScholarPubMed
35Clyne, B, Bradley, MC, Hughes, C, Fahey, T, Lapane, KL. Electronic prescribing and other forms of technology to reduce inappropriate medication use and polypharmacy in older people: a review of current evidence. Clin Geriatr Med 2012; 28: 301–22.CrossRefGoogle ScholarPubMed
36Peron, EP, Marcum, ZA, Boyce, R, Hanlon, JT, Handler, SM. Year in review: medication mishaps in the elderly. Am J Geriatr Pharmacother 2011; 9: 1–10.CrossRefGoogle ScholarPubMed
37Marcum, ZA, Pugh, MJ, Amuan, ME, Aspinall, SL, Handler, SM, Ruby, CMet al.Prevalence of potentially preventable unplanned hospitalizations caused by therapeutic failures and adverse drug withdrawal events among older veterans. J Gerontol A Biol Sci Med Sci 2012; 67: 867–74.CrossRefGoogle ScholarPubMed
38American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012; 60: 616–31.CrossRefGoogle Scholar
39Budnitz, DS, Shehab, N, Kegler, SR, Richards, CL. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med 2007; 147: 755–65.CrossRefGoogle ScholarPubMed
40Dettli, L. Drug dosage in renal disease. Clin Pharmacokinet 1976; 1: 126–34.CrossRefGoogle ScholarPubMed
41Denneboom, W, Dautzenberg, MG, Grol, R, De Smet, PA. Analysis of polypharmacy in older patients in primary care using a multidisciplinary expert panel. Br J Gen Pract 2006; 56: 504–10.Google ScholarPubMed
42Hanlon, JT, Aspinall, SL, Semla, TP, Weisbord, SD, Fried, LF, Good, CBet al.Consensus guidelines for oral dosing of primarily renally cleared medications in older adults. J Am Geriatr Soc 2009; 57: 335–40.CrossRefGoogle ScholarPubMed
43Hartmann, B, Czock, D, Keller, F. Drug therapy in patients with chronic renal failure. Dtsch Arztebl Int 2010; 107: 647–55; quiz 55–56.Google ScholarPubMed
44Peron, EP, Gray, SL, Hanlon, JT. Medication use and functional status decline in older adults: a narrative review. Am J Geriatr Pharmacother 2011; 9: 378–91.CrossRefGoogle ScholarPubMed
45Berdot, S, Bertrand, M, Dartigues, JF, Fourrier, A, Tavernier, B, Ritchie, Ket al.Inappropriate medication use and risk of falls – a prospective study in a large community-dwelling elderly cohort. BMC Geriatr 2009; 9: 30.Google Scholar
46Osterberg, L, Blaschke, T. Adherence to medication. N Engl J Med 2005; 353: 487–97.CrossRefGoogle ScholarPubMed
47Claxton, AJ, Cramer, J, Pierce, C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296–310.CrossRefGoogle ScholarPubMed
48Coleman, CI, Limone, B, Sobieraj, DM, Lee, S, Roberts, MS, Kaur, Ret al.Dosing frequency and medication adherence in chronic disease. J Manag Care Pharm 2012; 18: 527–39.Google ScholarPubMed
49Zedler, BK, Kakad, P, Colilla, S, Murrelle, L, Shah, NR. Does packaging with a calendar feature improve adherence to self-administered medication for long-term use? A systematic review. Clin Ther 2011; 33: 62–73.CrossRefGoogle ScholarPubMed
50Gardiner, SJ, Begg, EJ. Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev 2006; 58: 521–90.CrossRefGoogle ScholarPubMed
51Hylek, EM, Chang, YC, Skates, SJ, Hughes, RA, Singer, DE. Prospective study of the outcomes of ambulatory patients with excessive warfarin anticoagulation. Arch Intern Med 2000; 160: 1612–17.Google ScholarPubMed
52D’Andrea, G, D’Ambrosio, RL, Di Perna, P, Chetta, M, Santacroce, R, Brancaccio, Vet al.A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005; 105: 645–49.CrossRefGoogle Scholar
53Sandanaraj, E, Lal, S, Cheung, YB, Xiang, X, Kong, MC, Lee, LHet al.VKORC1 diplotype-derived dosing model to explain variability in warfarin dose requirements in Asian patients. Drug Metab Pharmacokinet 2009; 24: 365–75.CrossRefGoogle ScholarPubMed
54Klein, TE, Altman, RB, Eriksson, N, Gage, BF, Kimmel, SE, Lee, MTet al.Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360: 753–64.Google ScholarPubMed
55Manolopoulos, VG, Ragia, G, Tavridou, A. Pharmacogenetics of coumarinic oral anticoagulants. Pharmacogenomics 2010; 11: 493–96.CrossRefGoogle ScholarPubMed
56Mega, JL, Close, SL, Wiviott, SD, Shen, L, Walker, JR, Simon, Tet al.Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet 2010; 376: 1312–19.CrossRefGoogle Scholar
57Sugunaraj, JP, Palaniswamy, C, Selvaraj, DR, Chaitanya Arudra, SK, Sukhija, R. Clopidogrel resistance. Am J Ther 2010; 17: 210–15.CrossRefGoogle ScholarPubMed
58Sibbing, D, Gebhard, D, Koch, W, Braun, S, Stegherr, J, Morath, Tet al.Isolated and interactive impact of common CYP2C19 genetic variants on the antiplatelet effect of chronic clopidogrel therapy. J Thromb Haemost 2010; 8: 1685–93.CrossRefGoogle ScholarPubMed
59Ziegler, S, Schillinger, M, Funk, M, Felber, K, Exner, M, Mlekusch, Wet al.Association of a functional polymorphism in the clopidogrel target receptor gene, P2Y12, and the risk for ischemic cerebrovascular events in patients with peripheral artery disease. Stroke 2005; 36: 1394–99.CrossRefGoogle ScholarPubMed
60Harmsze, A, van Werkum, JW, Bouman, HJ, Ruven, HJ, Breet, NJ, Ten Berg, JMet al.Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenet Genomics 2010; 20: 18–25.CrossRefGoogle ScholarPubMed
61Staritz, P, Kurz, K, Stoll, M, Giannitsis, E, Katus, HA, Ivandic, BT. Platelet reactivity and clopidogrel resistance are associated with the H2 haplotype of the P2Y12-ADP receptor gene. Int J Cardiol 2009; 133: 341–45.CrossRefGoogle ScholarPubMed
62Giusti, B, Gori, AM, Marcucci, R, Saracini, C, Sestini, I, Paniccia, Ret al.Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10 + 12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients. Pharmacogenet Genomics 2007; 17: 1057–64.CrossRefGoogle Scholar
63Holmes, DR Jr, Dehmer, GJ, Kaul, S, Leifer, D, O’Gara, PT, Stein, CM. ACCF/AHA clopidogrel clinical alert: approaches to the FDA ‘boxed warning’: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 2010; 56: 321–41.CrossRefGoogle Scholar
64Sorich, MJ, Polasek, TM, Wiese, MD. Challenges and limitations in the interpretation of systematic reviews: making sense of clopidogrel and CYP2C19 pharmacogenetics. Clin Pharmacol Ther 2013; 94: 376–82.CrossRefGoogle ScholarPubMed
65Kawamura, M, Ohara, S, Koike, T, Iijima, K, Suzuki, H, Kayaba, Set al.Cytochrome P450 2C19 polymorphism influences the preventive effect of lansoprazole on the recurrence of erosive reflux esophagitis. J Gastroenterol Hepatol 2007; 22: 222–26.CrossRefGoogle ScholarPubMed
66Egan, LJ, Myhre, GM, Mays, DC, Dierkhising, RA, Kammer, PP, Murray, JA. CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms. Aliment Pharmacol Ther 2003; 17: 1521–28.CrossRefGoogle ScholarPubMed
67Furuta, T, Shirai, N, Ohashi, K, Ishizaki, T. Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori. Methods Find Exp Clin Pharmacol 2003; 25: 131–43.CrossRefGoogle ScholarPubMed
68Kang, JM, Kim, N, Lee, DH, Park, YS, Kim, JS, Chang, IJet al.Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage. J Gastroenterol Hepatol 2008; 23: 1287–91.CrossRefGoogle ScholarPubMed
69Kirchheiner, J, Muller, G, Meineke, I, Wernecke, KD, Roots, I, Brockmoller, J. Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. J Clin Psychopharmacol 2003; 23: 459–66.CrossRefGoogle ScholarPubMed
70Ellingrod, VL, Schultz, SK, Arndt, S. Association between cytochrome P4502D6 (CYP2D6) genotype, antipsychotic exposure, and abnormal involuntary movement scale (AIMS) score. Psychiatr Genet 2000; 10: 9–11.CrossRefGoogle ScholarPubMed
71Andreassen, OA, MacEwan, T, Gulbrandsen, AK, McCreadie, RG, Steen, VM. Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients. Psychopharmacology (Berl) 1997; 131: 174–79.CrossRefGoogle ScholarPubMed
72Borges, S, Desta, Z, Li, L, Skaar, TC, Ward, BA, Nguyen, Aet al.Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 2006; 80: 61–74.CrossRefGoogle ScholarPubMed
73Goetz, MP, Rae, JM, Suman, VJ, Safgren, SL, Ames, MM, Visscher, DWet al.Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 2005; 23: 9312–18.CrossRefGoogle ScholarPubMed
74Seripa, D, Bizzarro, A, Pilotto, A, D’Onofrio, G, Vecchione, G, Gallo, APet al.Role of cytochrome P4502D6 functional polymorphisms in the efficacy of donepezil in patients with Alzheimer's disease. Pharmacogenet Genomics 2011; 21: 225–30.Google ScholarPubMed
75Varsaldi, F, Miglio, G, Scordo, MG, Dahl, ML, Villa, LM, Biolcati, Aet al.Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer's disease patients. Eur J Clin Pharmacol 2006; 62: 721–26.CrossRefGoogle ScholarPubMed
76Caspi, A, Sugden, K, Moffitt, TE, Taylor, A, Craig, IW, Harrington, Het al.Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386–89.CrossRefGoogle ScholarPubMed
77Cervilla, JA, Rivera, M, Molina, E, Torres-Gonzalez, F, Bellon, JA, Moreno, Bet al.The 5-HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: the PREDICT-gene study. Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 912–17.CrossRefGoogle Scholar
78Lesch, KP, Bengel, D, Heils, A, Sabol, SZ, Greenberg, BD, Petri, Set al.Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–31.CrossRefGoogle ScholarPubMed
79Gerretsen, P, Pollock, BG. Pharmacogenetics and the serotonin transporter in late-life depression. Expert Opin Drug Metab Toxicol 2008; 4: 1465–78.CrossRefGoogle ScholarPubMed
80Heils, A, Teufel, A, Petri, S, Stober, G, Riederer, P, Bengel, Det al.Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621–24.CrossRefGoogle ScholarPubMed
81Vladutiu, GD, Isackson, PJ. SLCO1B1 variants and statin-induced myopathy. N Engl J Med 2009; 360: 304.CrossRefGoogle ScholarPubMed
82Medina, MW, Gao, F, Ruan, W, Rotter, JI, Krauss, RM. Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin. Circulation 2008; 118: 355–62.CrossRefGoogle Scholar
83Utermann, G. Apolipoprotein E polymorphism in health and disease. Am Heart J 1987; 113: 433–40.CrossRefGoogle ScholarPubMed
84Ruiz, JG, Array, S, Lowenthal, DT. Therapeutic drug monitoring in the elderly. Am J Ther 1996; 3: 839–60.CrossRefGoogle ScholarPubMed
85Ghiculescu, R. Therapeutic drug monitoring: which drugs, why, when and how to do it. Aust Prescr 2008; 31: 42–44.CrossRefGoogle Scholar
86Klotz, U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009; 41: 67–76.CrossRefGoogle ScholarPubMed
87Greenblatt, DJ, Harmatz, JS, Shader, RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part II). Clin Pharmacokinet 1991; 21: 262–73.CrossRefGoogle ScholarPubMed
88Lundmark, J, Bengtsson, F, Nordin, C, Reis, M, Walinder, J. Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients. Acta Psychiatr Scand 2000; 101: 354–59.CrossRefGoogle ScholarPubMed
89Bonetti, A, Franceschi, T, Apostoli, P, Cetto, GL, Recaldin, E, Molino, Aet al.Cisplatin pharmacokinetics in elderly patients. Ther Drug Monit 1994; 16: 477–82.CrossRefGoogle ScholarPubMed
90Greenblatt, DJ, Abernethy, DR, Shader, RI. Pharmacokinetic aspects of drug therapy in the elderly. Ther Drug Monit 1986; 8: 249–55.CrossRefGoogle ScholarPubMed
91Waade, RB, Molden, E, Refsum, H, Hermann, M. Serum concentrations of antidepressants in the elderly. Ther Drug Monit 2012; 34: 25–30.CrossRefGoogle ScholarPubMed