Pharmacokinetics and drug metabolism of antibiotics in the elderly

References

• Harper S. Economic and social implications of aging societies. Science. 2014;346:587–591.
   PubMed Web of Science ®Google Scholar
• Zarb P, Amadeo B, Muller A, et al. Antimicrobial prescribing in hospitalized adults stratified by age: data from the ESAC point-prevalence surveys. Drugs Aging. 2012;29:53–62.
   PubMed Web of Science ®Google Scholar
• Mouton CP, Bazaldua OV, Pierce B, et al. Common infections in older adults. Am Fam Physician. 2001;63:257–268.
   PubMed Web of Science ®Google Scholar
• Brauer R, Ruigomez A, Downey G, et al. Prevalence of antibiotic use: a comparison across various European health care data sources. Pharmacoepidemiol Drug Saf. 2016;25(Suppl 1):11–20.
   PubMedGoogle Scholar
• Daneman N, Bronskill SE, Gruneir A, et al. Variability in antibiotic use across nursing homes and the risk of antibiotic-related adverse outcomes for individual residents. JAMA Intern Med. 2015;175:1331–1339.
   PubMed Web of Science ®Google Scholar
• Pea F. Antimicrobial treatment of bacterial infections in frail elderly patients: the difficult balance between efficacy, safety and tolerability. Curr Opin Pharmacol. 2015;24:18–22.
   PubMed Web of Science ®Google Scholar
• Zamboni M, Rossi AP, Fantin F, et al. Adipose tissue, diet and aging. Mech Ageing Dev. 2014;136-137:129–137.
   PubMed Web of Science ®Google Scholar
• Tan JL, Eastment JG, Poudel A, et al. Age-related changes in hepatic function: an update on implications for drug therapy. Drugs Aging. 2015;32:999–1008.
   PubMed Web of Science ®Google Scholar
• Bolignano D, Mattace-Raso F, Sijbrands EJ, et al. The aging kidney revisited: a systematic review. Ageing Res Rev. 2014;14:65–80.
   PubMed Web of Science ®Google Scholar
• Cojutti P, Arnoldo L, Cattani G, et al. Polytherapy and the risk of potentially inappropriate prescriptions (PIPs) among elderly and very elderly patients in three different settings (hospital, community, long-term care facilities) of the Friuli Venezia Giulia region, Italy: are the very elderly at higher risk of PIPs? Pharmacoepidemiol Drug Saf. 2016;25:1070–1078.
   PubMed Web of Science ®Google Scholar
• Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158:869–876.
   PubMed Web of Science ®Google Scholar
• Parekh TM, Raji M, Lin YL, et al. Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas. JAMA Intern Med. 2014;174:1605–1612.
   PubMed Web of Science ®Google Scholar
• Baillargeon J, Holmes HM, Lin YL, et al. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med. 2012;125:183–189.
   PubMed Web of Science ®Google Scholar
• Mattappalil A, Mergenhagen KA. Neurotoxicity with antimicrobials in the elderly: a review. Clin Ther. 2014;36:1489–1511. e1484.
   PubMed Web of Science ®Google Scholar
• Imani S, Buscher H, Marriott D, et al. Too much of a good thing: a retrospective study of beta-lactam concentration-toxicity relationships. J Antimicrob Chemother. 2017;72:2891–2897.
   PubMed Web of Science ®Google Scholar
• Tannenbaum C, Day D. Age and sex in drug development and testing for adults. Pharmacol Res. 2017;121:83–93. .
   PubMed Web of Science ®Google Scholar
• Onysko M, Holcomb N, Hornecker J. Antibiotic interactions: answers to 4 common questions. J Fam Pract. 2016;65:442–448.
   PubMed Web of Science ®Google Scholar
• Petrosillo N, Cataldo MA, Pea F. Treatment options for community-acquired pneumonia in the elderly people. Expert Rev Anti Infect Ther. 2015;13:473–485.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Proposed working definition of an older person in Africa for the MDS project. [cited 2018 July 18]. Available from: http://www.who.int/healthinfo/survey/ageingdefnolder/en/2002
   Google Scholar
• Ramsay SE, Whincup PH, Shaper AG, et al. The relations of body composition and adiposity measures to ill health and physical disability in elderly men. Am J Epidemiol. 2006;164:459–469.
   PubMed Web of Science ®Google Scholar
• Klotz U, Avant GR, Hoyumpa A, et al. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest. 1975;55:347–359.
   PubMed Web of Science ®Google Scholar
• Cusack B, Kelly J, O’Malley K, et al. Digoxin in the elderly: pharmacokinetic consequences of old age. Clin Pharmacol Ther. 1979;25:772–776.
   PubMed Web of Science ®Google Scholar
• Meeuwsen S, Horgan GW, Elia M. The relationship between BMI and percent body fat, measured by bioelectrical impedance, in a large adult sample is curvilinear and influenced by age and sex. Clin Nutr. 2010;29:560–566.
   PubMed Web of Science ®Google Scholar
• Fulop T Jr., Worum I, Csongor J, et al. 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.
   PubMed Web of Science ®Google Scholar
• Baumgartner RN, Stauber PM, McHugh D, et al. Cross-sectional age differences in body composition in persons 60+ years of age. J Gerontol A Biol Sci Med Sci. 1995;50:M307–316.
   PubMed Web of Science ®Google Scholar
• Jain R, Chung SM, Jain L, et al. Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther. 2011;90:77–89.
   PubMed Web of Science ®Google Scholar
• Burris JF, Tortorici MA, Mandic M, et al. Dosage adjustments related to young or old age and organ impairment. J Clin Pharmacol. 2016;56:1461–1473.
   PubMed Web of Science ®Google Scholar
• Wynne HA, Cope LH, Mutch E, et al. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology. 1989;9:297–301.
   PubMed Web of Science ®Google Scholar
• Schmucker DL. Age-related changes in liver structure and function: implications for disease? Exp Gerontol. 2005;40:650–659.
   PubMed Web of Science ®Google Scholar
• Zoli M, Magalotti D, Bianchi G, et al. Total and functional hepatic blood flow decrease in parallel with ageing. Age Ageing. 1999;28:29–33.
   PubMed Web of Science ®Google Scholar
• Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther. 1997;61:331–339.
   PubMed Web of Science ®Google Scholar
• Cotreau MM, von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet. 2005;44:33–60.
   PubMed Web of Science ®Google Scholar
• Castleden CM, George CF. The effect of ageing on the hepatic clearance of propranolol. Br J Clin Pharmacol. 1979;7:49–54.
   PubMed Web of Science ®Google Scholar
• Elliott HL, Meredith PA, Reid JL, et al. A comparison of the disposition of single oral doses of amlodipine in young and elderly subjects. J Cardiovasc Pharmacol. 1988;12(Suppl 7):S64–66.
   PubMedGoogle Scholar
• Schwartz JB, Abernethy DR. Responses to intravenous and oral diltiazem in elderly and younger patients with systemic hypertension. Am J Cardiol. 1987;59:1111–1117.
   PubMed Web of Science ®Google Scholar
• Yoshida K, Sun B, Zhang L, et al. Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5. Clin Pharmacol Ther. 2016;100:75–87.
   PubMed Web of Science ®Google Scholar
• Herd B, Wynne H, Wright P, et al. The effect of age on glucuronidation and sulphation of paracetamol by human liver fractions. Br J Clin Pharmacol. 1991;32:768–770.
   PubMed Web of Science ®Google Scholar
• Kinirons MT, O’Mahony MS. Drug metabolism and ageing. Br J Clin Pharmacol. 2004;57:540–544.
   PubMed Web of Science ®Google Scholar
• Pea F, Pavan F, Lugatti E, et al. Pharmacokinetic and pharmacodynamic aspects of oral moxifloxacin 400 mg/day in elderly patients with acute exacerbation of chronic bronchitis. Clin Pharmacokinet. 2006;45:287–295.
   PubMed Web of Science ®Google Scholar
• Wynne H. Drug metabolism and ageing. J Br Menopause Soc. 2005;11:51–56.
   PubMedGoogle Scholar
• Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet. 2013;381:752–762.
   PubMed Web of Science ®Google Scholar
• Huisman-Baron M, van der Veen L, Jansen PA, et al. Criteria for drug selection in frail elderly persons. Drugs Aging. 2011;28:391–402.
   PubMed Web of Science ®Google Scholar
• Wynne HA, Cope LH, Herd B, et al. The association of age and frailty with paracetamol conjugation in man. Age Ageing. 1990;19:419–424.
   PubMed Web of Science ®Google Scholar
• Hollenberg NK, Adams DF, Solomon HS, et al. Senescence and the renal vasculature in normal man. Circ Res. 1974;34:309–316.
   PubMed Web of Science ®Google Scholar
• Fehrman-Ekholm I, Skeppholm L. Renal function in the elderly (>70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance. Scand J Urol Nephrol. 2004;38:73–77.
   PubMed Web of Science ®Google Scholar
• Ciarambino T, Paolo C, Giordano M. Age and frailty: are they related in decline of renal function? J Gerontol Geriatr. 2017;65:161–168.
   Web of Science ®Google Scholar
• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.
   PubMed Web of Science ®Google Scholar
• Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.
   PubMed Web of Science ®Google Scholar
• Drenth-van Maanen AC, Jansen PA, Proost JH, et al. Renal function assessment in older adults. Br J Clin Pharmacol. 2013;76:616–623.
   PubMed Web of Science ®Google Scholar
• Whitley H, Lindsey W. Sex-based differences in drug activity. Am Fam Physician. 2009;80:1254–1258.
   PubMed Web of Science ®Google Scholar
• Easton J, Noble S, Perry CM. Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media. Drugs. 2003;63:311–340.
   PubMed Web of Science ®Google Scholar
• Foulds G, Knirsch AK, Stankewich JP, et al. The parenteral kinetics of ampicillin/sulbactam in man. Int J Clin Pharmacol Res. 1985;5:79–86.
   PubMedGoogle Scholar
• Nauta EH, Mattie H. Pharmacokinetics of flucloxacillin and cloxacillin in healthy subjects and patients on chronic intermittent haemodialysis. Br J Clin Pharmacol. 1975;2:111–121.
   PubMed Web of Science ®Google Scholar
• Bryson HM, Brogden RN. Piperacillin/tazobactam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential. Drugs. 1994;47:506–535.
   PubMed Web of Science ®Google Scholar
• Brogden RN, Spencer CM. Cefotaxime. A reappraisal of its antibacterial activity and pharmacokinetic properties, and a review of its therapeutic efficacy when administered twice daily for the treatment of mild to moderate infections. Drugs. 1997;53:483–510.
   PubMed Web of Science ®Google Scholar
• Lenfant B, Namour F, Logeais C, et al. Pharmacokinetics of cefodizime following single doses of 0.5, 1.0, 2.0, and 3.0 grams administered intravenously to healthy volunteers. Antimicrob Agents Chemother. 1995;39:2037–2041.
   PubMed Web of Science ®Google Scholar
• Lamb HM, Ormrod D, Scott LJ, et al. Ceftriaxone: an update of its use in the management of community-acquired and nosocomial infections. Drugs. 2002;62:1041–1089.
   PubMed Web of Science ®Google Scholar
• Riccobene T, Jakate A, Rank D. A series of pharmacokinetic studies of ceftaroline fosamil in select populations: normal subjects, healthy elderly subjects, and subjects with renal impairment or end-stage renal disease requiring hemodialysis. J Clin Pharmacol. 2014;54:742–752.
   PubMed Web of Science ®Google Scholar
• Torres A, Mouton JW, Pea F. Pharmacokinetics and dosing of ceftobiprole medocaril for the treatment of hospital- and community-acquired pneumonia in different patient populations. Clin Pharmacokinet. 2016;55:1507–1520.
   PubMed Web of Science ®Google Scholar
• Kozawa O, Uematsu T, Matsuno H, et al. Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in elderly subjects. Antimicrob Agents Chemother. 1998;42:1433–1436.
   PubMed Web of Science ®Google Scholar
• Nix DE, Majumdar AK, DiNubile MJ. Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians. J Antimicrob Chemother. 2004;53(Suppl 2):ii23–28.
   PubMed Web of Science ®Google Scholar
• Dreetz M, Hamacher J, Eller J, et al. Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin. Antimicrob Agents Chemother. 1996;40:105–109.
   PubMed Web of Science ®Google Scholar
• Adamis G, Papaioannou MG, Giamarellos-Bourboulis EJ, et al. Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers. Int J Antimicrob Agents. 2004;23:144–149.
   PubMed Web of Science ®Google Scholar
• Gyselynck AM, Forrey A, Cutler R. Pharmacokinetics of gentamicin: distribution and plasma and renal clearance. J Infect Dis. 1971;124(Suppl):S70–76.
   PubMedGoogle Scholar
• Davis R, Markham A, Balfour JA. Ciprofloxacin. An updated review of its pharmacology, therapeutic efficacy and tolerability. Drugs. 1996;51:1019–1074.
   PubMed Web of Science ®Google Scholar
• Anderson VR, Perry CM. Levofloxacin: a review of its use as a high-dose, short-course treatment for bacterial infection. Drugs. 2008;68:535–565.
   PubMed Web of Science ®Google Scholar
• Keating GM, Scott LJ. Moxifloxacin: a review of its use in the management of bacterial infections. Drugs. 2004;64:2347–2377.
   PubMed Web of Science ®Google Scholar
• Zhanel GG, Dueck M, Hoban DJ, et al. Review of macrolides and ketolides: focus on respiratory tract infections. Drugs. 2001;61:443–498.
   PubMed Web of Science ®Google Scholar
• Suzuki A, Iida I, Hirota M, et al. CYP isoforms involved in the metabolism of clarithromycin in vitro: comparison between the identification from disappearance rate and that from formation rate of metabolites. Drug Metab Pharmacokinet. 2003;18:104–113.
   PubMedGoogle Scholar
• Wellington K, Noble S. Telithromycin. Drugs. 2004;64:1683–1694. discussion 1695-1686
   PubMed Web of Science ®Google Scholar
• Van Bambeke F, Van Laethem Y, Courvalin P, et al. Glycopeptide antibiotics: from conventional molecules to new derivatives. Drugs. 2004;64:913–936.
   PubMed Web of Science ®Google Scholar
• Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006;58:256–265.
   PubMed Web of Science ®Google Scholar
• Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005;40:1333–1341.
   PubMed Web of Science ®Google Scholar
• Tedesco KL, Rybak MJ. Daptomycin. Pharmacotherapy. 2004;24:41–57.
   PubMed Web of Science ®Google Scholar
• Sastry S, Doi Y. Fosfomycin: resurgence of an old companion. J Infect Chemother. 2016;22:273–280.
   PubMed Web of Science ®Google Scholar
• Slatter JG, Stalker DJ, Feenstra KL, et al. Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [(14)C]linezolid to healthy human subjects. Drug Metab Dispos. 2001;29:1136–1145.
   PubMed Web of Science ®Google Scholar
• Lamp KC, Freeman CD, Klutman NE, et al. Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin Pharmacokinet. 1999;36:353–373.
   PubMed Web of Science ®Google Scholar
• Kenny MT, Strates B. Metabolism and pharmacokinetics of the antibiotic rifampin. Drug Metab Rev. 1981;12:159–218.
   PubMed Web of Science ®Google Scholar
• Lyseng-Williamson KA, Blick SK. Telavancin. Drugs. 2009;69:2607–2620.
   PubMed Web of Science ®Google Scholar
• Hines LE, Murphy JE. Potentially harmful drug-drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011;9:364–377.
   PubMed Web of Science ®Google Scholar
• Cojutti P, Pai MP, Pea F. Population pharmacokinetics and dosing considerations for the use of linezolid in overweight and obese adult patients. Clin Pharmacokinet. 2018;57:989–1000.
   Web of Science ®Google Scholar
• Pea F, Cojutti PG, Baraldo M. A 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a hospital-wide population of patients receiving conventional dosing: is there enough evidence for suggesting TDM in the majority of patients? Basic Clin Pharmacol Toxicol. 2017;121:303–308.
   PubMed Web of Science ®Google Scholar
• Janknegt R, Boogaard-Van Den Born J, Hameleers BA, et al. Pharmacokinetics of amoxycillin in elderly in-patients. Pharm Weekbl Sci. 1992;14:27–29.
   PubMedGoogle Scholar
• Majcher-Peszynska J, Loebermann M, Klammt S, et al. Ampicillin/sulbactam in elderly patients with community-acquired pneumonia. Infection. 2014;42:79–87.
   PubMed Web of Science ®Google Scholar
• Gath J, Charles B, Sampson J, et al. Pharmacokinetics and bioavailability of flucloxacillin in elderly hospitalized patients. J Clin Pharmacol. 1995;35:31–36.
   PubMed Web of Science ®Google Scholar
• Ljungberg B, Nilsson-Ehle I. Comparative pharmacokinetics of ceftazidime in young, healthy and elderly, acutely ill males. Eur J Clin Pharmacol. 1988;34:179–186.
   PubMed Web of Science ®Google Scholar
• Urien S, Laurent N, Barre J, et al. Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime–a population study in 25 elderly patients. Eur J Clin Pharmacol. 2004;60:11–16.
   PubMed Web of Science ®Google Scholar
• Meyer B, Traunmueller F, Bojic A, et al. Single-dose pharmacokinetics of cefodizime in critically ill elderly patients. Int J Antimicrob Agents. 2006;27:335–338.
   PubMed Web of Science ®Google Scholar
• Bryskier A, Procyk T, Tremblay D, et al. Pharmacokinetics of cefodizime administered intravenously as a single-dose (1.0 and 2.0 g) to healthy adult volunteers. J Antimicrob Chemother. 1990;26(Suppl C):65–70.
   PubMedGoogle Scholar
• Namkoong H, Kameyama Y, Yasuda H, et al. The efficacy, safety, and pharmacokinetics of biapenem administered thrice daily for the treatment of pneumonia in the elderly. J Infect Chemother. 2014;20:356–360.
   PubMed Web of Science ®Google Scholar
• Koeppe P, Hoffler D, Fitzen B. Biapenem pharmacokinetics in healthy volunteers and in patients with impaired renal function. Arzneimittelforschung. 1997;47:1250–1256.
   PubMed Web of Science ®Google Scholar
• Musson DG, Majumdar A, Holland S, et al. Pharmacokinetics of total and unbound ertapenem in healthy elderly subjects. Antimicrob Agents Chemother. 2004;48:521–524.
   PubMed Web of Science ®Google Scholar
• Zhou QT, He B, Zhang C, et al. Pharmacokinetics and pharmacodynamics of meropenem in elderly Chinese with lower respiratory tract infections: population pharmacokinetics analysis using nonlinear mixed-effects modelling and clinical pharmacodynamics study. Drugs Aging. 2011;28:903–912.
   PubMed Web of Science ®Google Scholar
• Usman M, Frey OR, Hempel G. Population pharmacokinetics of meropenem in elderly patients: dosing simulations based on renal function. Eur J Clin Pharmacol. 2017;73:333–342. .
   PubMed Web of Science ®Google Scholar
• Krueger WA, Bulitta J, Kinzig-Schippers M, et al. Evaluation by Monte Carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers. Antimicrob Agents Chemother. 2005;49:1881–1889.
   PubMed Web of Science ®Google Scholar
• Pea F, Della Siega P, Cojutti P, et al. Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae? Int J Antimicrob Agents. 2017;49:255–258.
   PubMed Web of Science ®Google Scholar
• Lee CR, Lee JH, Park KS, et al. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;7:895.
   PubMed Web of Science ®Google Scholar
• Cojutti P, Sartor A, Righi E, et al. Population pharmacokinetics of high-dose continuous-infusion meropenem and considerations for use in the treatment of infections due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2017;61. DOI:10.1128/aac.00794-17.
   Web of Science ®Google Scholar
• Franceschi L, Cojutti P, Baraldo M, et al. Stability of generic meropenem solutions for administration by continuous infusion at normal and elevated temperatures. Ther Drug Monit. 2014;36:674–676.
   PubMed Web of Science ®Google Scholar
• Debord J, Charmes JP, Marquet P, et al. Population pharmacokinetics of amikacin in geriatric patients studied with the NPEM-2 algorithm. Int J Clin Pharmacol Ther. 1997;35:24–27.
   PubMed Web of Science ®Google Scholar
• Garraffo R, Drugeon HB, Dellamonica P, et al. Determination of optimal dosage regimen for amikacin in healthy volunteers by study of pharmacokinetics and bactericidal activity. Antimicrob Agents Chemother. 1990;34:614–621.
   PubMed Web of Science ®Google Scholar
• Hilmer SN, Tran K, Rubie P, et al. Gentamicin pharmacokinetics in old age and frailty. Br J Clin Pharmacol. 2011;71:224–231.
   PubMed Web of Science ®Google Scholar
• Johnston C, Hilmer SN, McLachlan AJ, et al. The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration. Eur J Clin Pharmacol. 2014;70:549–555.
   PubMed Web of Science ®Google Scholar
• Molinaro M, Villani P, Regazzi MB, et al. Pharmacokinetics of ofloxacin in elderly patients and in healthy young subjects. Eur J Clin Pharmacol. 1992;43:105–107.
   PubMed Web of Science ®Google Scholar
• Cios A, Wyska E, Szymura-Oleksiak J, et al. Population pharmacokinetic analysis of ciprofloxacin in the elderly patients with lower respiratory tract infections. Exp Gerontol. 2014;57:107–113.
   PubMed Web of Science ®Google Scholar
• Gonzalez MA, Moranchel AH, Duran S, et al. Multiple-dose pharmacokinetics of ciprofloxacin administered intravenously to normal volunteers. Antimicrob Agents Chemother. 1985;28:235–239.
   PubMed Web of Science ®Google Scholar
• Cojutti PG, Ramos-Martin V, Schiavon I, et al. Population pharmacokinetics and pharmacodynamics of levofloxacin in acutely hospitalized older patients with various degrees of renal function. Antimicrob Agents Chemother. 2017;61. DOI:10.1128/aac.02134-16.
   Web of Science ®Google Scholar
• Chow AT, Fowler C, Williams RR, et al. Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers. Antimicrob Agents Chemother. 2001;45:2122–2125.
   PubMed Web of Science ®Google Scholar
• Stass H, Dalhoff A, Kubitza D, et al. Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxy quinolone, administered to healthy subjects. Antimicrob Agents Chemother. 1998;42:2060–2065.
   PubMed Web of Science ®Google Scholar
• Le Couteur DG, McLean AJ. The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet. 1998;34:359–373.
   PubMed Web of Science ®Google Scholar
• Chu SY, Wilson DS, Guay DR, et al. Clarithromycin pharmacokinetics in healthy young and elderly volunteers. J Clin Pharmacol. 1992;32:1045–1049.
   PubMed Web of Science ®Google Scholar
• Shi J, Montay G, Bhargava VO. Clinical pharmacokinetics of telithromycin, the first ketolide antibacterial. Clin Pharmacokinet. 2005;44:915–934.
   PubMed Web of Science ®Google Scholar
• Rosina R, Villa G, Danese A, et al. Pharmacokinetics of teicoplanin in the elderly. J Antimicrob Chemother. 1988;21(Suppl A):39–45.
   PubMedGoogle Scholar
• Glatard A, Bourguignon L, Jelliffe RW, et al. Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients. Antimicrob Agents Chemother. 2015;59:2986–2994.
   PubMed Web of Science ®Google Scholar
• Bourguignon L, Cazaubon Y, Debeurme G, et al. Pharmacokinetics of vancomycin in elderly patients aged over 80 years. Antimicrob Agents Chemother. 2016;60:4563–4567. .
   PubMed Web of Science ®Google Scholar
• Abe S, Chiba K, Cirincione B, et al. Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients. J Clin Pharmacol. 2009;49:1071–1078.
   PubMed Web of Science ®Google Scholar
• Loft S, Egsmose C, Sonne J, et al. Metronidazole elimination is preserved in the elderly. Hum Exp Toxicol. 1990;9:155–159.
   PubMed Web of Science ®Google Scholar
• Varoquaux O, Lajoie D, Gobert C, et al. Pharmacokinetics of the trimethoprim-sulphamethoxazole combination in the elderly. Br J Clin Pharmacol. 1985;20:575–581.
   PubMed Web of Science ®Google Scholar
• Goldberg MR, Wong SL, Shaw JP, et al. Single-dose pharmacokinetics and tolerability of telavancin in elderly men and women. Pharmacotherapy. 2010;30:806–811.
   PubMed Web of Science ®Google Scholar
• Muralidharan G, Fruncillo RJ, Micalizzi M, et al. Effects of age and sex on single-dose pharmacokinetics of tigecycline in healthy subjects. Antimicrob Agents Chemother. 2005;49:1656–1659.
   PubMed Web of Science ®Google Scholar
• Corsonello A, Pedone C, Corica F, et al. Concealed renal insufficiency and adverse drug reactions in elderly hospitalized patients. Arch Intern Med. 2005;165:790–795.
   PubMedGoogle Scholar
• Elinder CG, Barany P, Heimburger O. The use of estimated glomerular filtration rate for dose adjustment of medications in the elderly. Drugs Aging. 2014;31:493–499.
   PubMed Web of Science ®Google Scholar
• Triggs E, Charles B. Pharmacokinetics and therapeutic drug monitoring of gentamicin in the elderly. Clin Pharmacokinet. 1999;37:331–341.
   PubMed Web of Science ®Google Scholar
• Oh SJ, Hong KS, Lee EJ, et al. Assessment of therapeutic drug monitoring of vancomycin in elderly patients according to new guidelines. Ann Lab Med. 2014;34:1–6.
   PubMed Web of Science ®Google Scholar
• Cattaneo D, Gervasoni C, Cozzi V, et al. Therapeutic drug management of linezolid: a missed opportunity for clinicians? Int J Antimicrob Agents. 2016;48:728–731.
   PubMed Web of Science ®Google Scholar
• Huttner A, Harbarth S, Hope WW, et al. Therapeutic drug monitoring of the β-lactam antibiotics: what is the evidence and which patients should we be using it for? J Antimicrob Chemother. 2015;70:3178–3183.
   PubMed Web of Science ®Google Scholar
• Patel NS, Patel TK, Patel PB, et al. Hospitalizations due to preventable adverse reactions-a systematic review. Eur J Clin Pharmacol. 2017;73:385–398.
   PubMed Web of Science ®Google Scholar
• Budnitz DS, Lovegrove MC, Shehab N, et al. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365:2002–2012.
   PubMed Web of Science ®Google Scholar
• Garasto S, Fusco S, Corica F, et al. Estimating glomerular filtration rate in older people. BioMed Research International. 2014;2014:916542.
   PubMedGoogle Scholar
• Hubbard RE, O’Mahony MS, Woodhouse KW. Medication prescribing in frail older people. Eur J Clin Pharmacol. 2013;69:319–326.
   PubMed Web of Science ®Google Scholar
• Pea F, Cojutti P, Tursi V, et al. Everolimus overexposure in a heart transplant patient receiving clarithromycin for the treatment of pneumonia. Transpl Infect Dis. 2015;17:926–928.
   PubMed Web of Science ®Google Scholar
• Corsonello A, Abbatecola AM, Fusco S, et al. The impact of drug interactions and polypharmacy on antimicrobial therapy in the elderly. Clin Microbiol Infect. 2015;21:20–26.
   PubMed Web of Science ®Google Scholar
• Zhou QT, He B, Shen N, et al. Meropenem dosing based on a population pharmacokinetic-pharmacodynamic model in elderly patients with infection of the lower respiratory tract. Drugs Aging. 2017;34:115–121.
   PubMed Web of Science ®Google Scholar