1,480
Views
29
CrossRef citations to date
0
Altmetric
Review

Alterations in drug disposition in older adults: a focus on geriatric syndromes

, , , &
Pages 41-52 | Received 02 Aug 2020, Accepted 16 Oct 2020, Published online: 02 Nov 2020

References

  • World Health Organization. World report on ageing and health. Geneva, Switzerland: World Health Organization; 2015.
  • Moore KL, Patel K, John Boscardin W, et al. Medication burden attributable to chronic comorbid conditions in the very old and vulnerable. PLoS One. 2018;13(4):e0196109.
  • Gnjidic D, Hilmer SN, Blyth FM, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol. 2012;65(9):989–995.
  • Davies LE, Spiers G, Kingston A, et al. Adverse outcomes of polypharmacy in older people: systematic review of reviews. J Am Med Dir Assoc. 2020;21(2):181–187.
  • Ruiter R, Burggraaf J, Rissmann R. Under-representation of elderly in clinical trials: an analysis of the initial approval documents in the food and drug administration database. Br J Clin Pharmacol. 2019;85(4):838–844.
  • Fialova D, Laffon B, Marinkovic V, et al. Medication use in older patients and age-blind approach: narrative literature review (insufficient evidence on the efficacy and safety of drugs in older age, frequent use of PIMs and polypharmacy, and underuse of highly beneficial nonpharmacological strategies). Eur J Clin Pharmacol. 2019;75(4):451–466.
  • Chetty M, Johnson TN, Polak S, et al. Physiologically based pharmacokinetic modelling to guide drug delivery in older people. Adv Drug Deliv Rev. 2018;135:85–96.
  • Reeve E, Wiese MD, Mangoni AA. Alterations in drug disposition in older adults. Expert Opin Drug Metab Toxicol. 2015;11(4):491–508.
  • Hartmanshenn C, Scherholz M, Androulakis IP. Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine. J Pharmacokinet Pharmacodyn. 2016;43(5):481–504.
  • Hamczyk MR, Nevado RM, Barettino A, et al. Biological Versus Chronological Aging JACC Focus Seminar. J Am Coll Cardiol. 2020;75(8):919–930.
  • Magnuson A, Sattar S, Nightingale G, et al. A practical guide to geriatric syndromes in older adults with cancer: a focus on falls, cognition, polypharmacy, and depression. Am. 2019;39:e96–e109.
  • Inouye SK, Studenski S, Tinetti ME, et al. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007;55(5):780–791.
  • Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41(2):67–76.
  • Drenth-van Maanen AC, Wilting I, Jansen PAF. Prescribing medicines to older people-How to consider the impact of ageing on human organ and body functions. Br J Clin Pharmacol. 2019;19:19.
  • Soenen S, Rayner CK, Jones KL, et al. The ageing gastrointestinal tract. Curr Opin Clin Nutr Metab Care. 2016;19(1):12–18.
  • Abuhelwa AY, Williams DB, Upton RN, et al. Food, gastrointestinal pH, and models of oral drug absorption. Eur J Pharm Biopharm. 2017;112:234–248.
  • Patel D, Bertz R, Ren S, et al. Review of gastric acid-reducing agent-mediated drug-drug interactions with orally administered medications. Clin Pharmacokinet. 2020;59(4):447–462.
  • Dumic I, Nordin T, Jecmenica M, et al. Gastrointestinal tract disorders in older age. Can J Gastroenterol Hepatol. 2019;2019:6757524.
  • Merchant HA, Liu F, Orlu Gul M, et al. Age-mediated changes in the gastrointestinal tract. Int J Pharm. 2016;512(2):382–395.
  • Russell RM. Changes in gastrointestinal function attributed to aging. Am J Clin Nutr. 1992;55(6Suppl):1203S–7S.
  • Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14.
  • Thurmann PA. Pharmacodynamics and pharmacokinetics in older adults. Curr Opin Anaesthesiol. 2020;33(1):109–113.
  • Jain R, Chung S, Jain L, et al. Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther. 2011;90(1):77–89.
  • Grandison MK, Boudinot FD. Age-related changes in protein binding of drugs - Implications for therapy. Clin Pharmacokinet. 2000;38(3):271–290.
  • Dasgupta A. Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in patient management. Clin Chim Acta. 2007;377(1–2):1–13.
  • Krishna DR, Klotz U. Extrahepatic metabolism of drugs in humans. Clin Pharmacokinet. 1994;26(2):144–160.
  • 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(12):999–1008.
  • Stader F, Siccardi M, Battegay M, et al. Repository describing an aging population to inform physiologically based pharmacokinetic models considering anatomical, physiological, and biological age-dependent changes. Clin Pharmacokinet. 2019;58(4):483–501.
  • Butler JM, Begg EJ. Free drug metabolic clearance in elderly people. Clin Pharmacokinet. 2008;47(5):297–321.
  • Waring RH, Harris RM, Mitchell SC. Drug metabolism in the elderly: A multifactorial problem? Maturitas. 2017;100:27–32.
  • Polasek TM, Patel F, Jensen BP, et al. Predicted metabolic drug clearance with increasing adult age. Br J Clin Pharmacol. 2013;75(4):1019–1028.
  • Cohen E, Nardi Y, Krause I, et al. A longitudinal assessment of the natural rate of decline in renal function with age. J Nephrol. 2014;27(6):635–641.
  • Bolignano D, Mattace-Raso F, Sijbrands EJG, et al. The aging kidney revisited: A systematic review. Ageing Res Rev. 2014;14:65–80.
  • Denic A, Glassock RJ, Rule AD. Structural and functional changes with the aging kidney. Adv Chronic Kidney Dis. 2016;23(1):19–28.
  • Pea F. Pharmacokinetics and drug metabolism of antibiotics in the elderly. Expert Opin Drug Metab Toxicol. 2018;14(10):1087–1100.
  • 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(1):75–87.
  • Dreisbach AW, Lertora JJ. The effect of chronic renal failure on drug metabolism and transport. Expert Opin Drug Metab Toxicol. 2008;4(8):1065–1074.
  • Tan ML, Yoshida K, Zhao P, et al. Effect of Chronic kidney disease on nonrenal elimination pathways: a systematic assessment of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP. Clin Pharmacol Ther. 2018;103(5):854–867.
  • Clegg A, Young J, Iliffe S, et al. Frailty in elderly people: Europe PMC funders; 2013.
  • Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol Ser A. 2007;62(7):722–727.
  • Hilmer SN, Wu H, Zhang M. Biology of frailty: implications for clinical pharmacology and drug therapy in frail older people. Mech Ageing Dev. 2019;181:22–28.
  • Hubbard RE, O’Mahony MS, Savva GM, et al. Inflammation and frailty measures in older people. J Cell Mol Med. 2009;13(9b):3103–3109.
  • Chang SS, Weiss CO, Xue QL, et al. Association between inflammatory-related disease burden and frailty: results from the women’s health and aging studies (WHAS) I and II. Arch Gerontol Geriatr. 2012;54:9–15.
  • Hughes K, Lang J, Lazare R, et al. Measurement of oxybutynin and its N-desethyl metabolite in plasma, and its application to pharmacokinetic studies in young, elderly and frail elderly volunteers. Xenobiotica. 1992;22(7):859–869.
  • Van Tongeren SP, Slaets JPJ, Harmsen HJM, et al. Fecal microbiota composition and frailty. Appl Environ Microbiol. 2005;71:6438–6442.
  • Marzetti E, Calvani R, Tosato M, et al. Sarcopenia: an overview. Aging Clin Exp Res. 2017;29(1):11–17.
  • Buch A, Carmeli E, Boker LK, et al. Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age—an overview. Exp Gerontol. 2016;76:25–32.
  • Hilmer SN, Tran K, Rubie P, et al. Gentamicin pharmacokinetics in old age and frailty. Br J Clin Pharmacol. 2011;71:224–231.
  • Le Couteur DG, Blyth FM, Creasey HM, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci. 2010;65:712–717.
  • Hubbard RE, O’Mahony MS, Calver BL, et al. Nutrition, inflammation, and leptin levels in aging and frailty. J Am Geriatr Soc. 2008;56:279–284.
  • Israili ZH, Dayton PG. HUMAN ALPHA-1-GLYCOPROTEIN AND ITS INTERACTIONS WITH DRUGS †,‡. Drug Metab Rev. 2001;33:161–235.
  • Reeve E, Trenaman SC, Rockwood K, et al. Pharmacokinetic and pharmacodynamic alterations in older people with dementia. Expert Opin Drug Metab Toxicol. 2017;13(6):651–668.
  • Roberts J, Pea F, Lipman J. The clinical relevance of plasma protein binding changes. Clin Pharmacokinet. 2013;52:1–8.
  • Morgan E. Impact of infectious and inflammatory disease on cytochrome P450–mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther. 2009;85(4):434–438.
  • Hubbard RE, O’Mahony MS, Calver BL, et al. Plasma esterases and inflammation in ageing and frailty. Eur J Clin Pharmacol. 2008;64:895–900.
  • Abou-Hatab K, O’Mahony MS, Patel S, et al. Relationship between age and plasma esterases. Age Ageing. 2001;30:41–45.
  • Dumond J, Chen J, Cottrell M, et al. Population pharmacokinetics modeling of unbound Efavirenz, Atazanavir, and Ritonavir in HIV-infected subjects with aging biomarkers. CPT Pharmacometrics Syst Pharmacol. 2017;6(2):128–135.
  • Wynne H. Drug metabolism and ageing. J Br Menopause Soc. 2005;11:51–56.
  • Wynne H, Cope LH, Herd B, et al. The association of age and frailty with paracetamol conjugation in man. Age Ageing. 1990;19:419–424.
  • Wynne HA, Yelland C, Cope LH, et al. The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide. Age Ageing. 1993;22:354–360.
  • 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.
  • Shlipak MG, Stehman-Breen C, Fried LF, et al. The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis. 2004;43:861–867.
  • Kane AE, Mitchell SJ, Mach J, et al. Acetaminophen hepatotoxicity in mice: effect of age, frailty and exposure type. Exp Gerontol. 2016;73:95–106.
  • Mitchell SJ, Hilmer SN, Murnion BP, et al. Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty. J Clin Pharm Ther. 2011;36:327–335.
  • Cullinan S, O’Mahony D, O’Sullivan D, et al. Use of a frailty index to identify potentially inappropriate prescribing and adverse drug reaction risks in older patients. Age Ageing. 2016;45:115–120.
  • Herr M, Robine J-M, Pinot J, et al. Polypharmacy and frailty: prevalence, relationship, and impact on mortality in a French sample of 2350 old people. Pharmacoepidemiol Drug Saf. 2015;24:637–646.
  • Bonaga B, Sánchez-Jurado PM, Martínez-Reig M, et al. Frailty, polypharmacy, and health outcomes in older adults: the frailty and dependence in albacete study. J Am Med Dir Assoc. 2018;19:46–52.
  • Porter B, Arthur A, Savva GM. How do potentially inappropriate medications and polypharmacy affect mortality in frail and non-frail cognitively impaired older adults? A cohort study. BMJ Open. 2019;9:5.
  • Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing. 2019;48:16–31.
  • Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019;393(10191):2636–2646.
  • Williams GR, Deal AM, Shachar SS, et al. The impact of skeletal muscle on the pharmacokinetics and toxicity of 5-fluorouracil in colorectal cancer. Cancer Chemother Pharmacol. 2018;81(2):413–417.
  • Vergara-Fernandez O, Trejo-Avila M, Salgado-Nesme N. Sarcopenia in patients with colorectal cancer: A comprehensive review. World J Clin Cases. 2020;8(7):1188–1202.
  • Association As. Alzheimer’s disease facts and figures. Alzheimer’s Dementia. 2015;2015(11):332–384.
  • Jin L, Pan Y, Tran NLL, et al. Intestinal permeability and oral absorption of selected drugs are reduced in a mouse model of familial Alzheimer’s disease. Mol Pharm. 2020;17(5):1527–1537.
  • Pan Y, Omori K, Ali I, et al. Altered expression of small intestinal drug transporters and hepatic metabolic enzymes in a mouse model of familial Alzheimer’s disease. Mol Pharm. 2018;15(9):4073–4083.
  • Ahmed AIA, Van Den Elsen GAH, Colbers A, et al. Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. Psychopharmacology (Berl). 2015;232:2587–2595.
  • Polinsky RJ. Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of alzheimer’s disease. Clin Ther. 1998;20(4):634–647.
  • Gillette Guyonnet SAVKG, Alix E, Andrieu S, et al. International Academy on Nutrition and Aging Expert Group. IANA (International Academy on Nutrition and Aging) expert group: weight loss and Alzheimer’s disease. J Nutr Health Aging. 2007;11:38–48.
  • Maes M, DeVos N, Wauters A, et al. Inflammatory markers in younger vs elderly normal volunteers and in patients with Alzheimer’s disease. J Psychiatr Res. 1999;33:397–405.
  • Duarte P, Duarte M, Pelichek A, et al. Cardiovascular risk factors and inflammatory activity among centenarians with and without dementia. Aging Clin Exp Res. 2017 Jun;29(3):411–417.
  • Zhang R, Barker L, Pinchev D, et al. Mining biomarkers in human sera using proteomic tools. Proteomics. 2004;4:244–256.
  • German DC, Gurnani P, Nandi A, et al. Serum biomarkers for Alzheimer’s disease: proteomic discovery. Biomed Pharmacothe. 2007;61:383–389.
  • Blood-brain barrier: ageing and microvascular disease - systematic review and meta-analysis; 2009.
  • Janelidze S, Hertze J, Nägga K, et al. Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype. Neurobiol Aging. 2017;51:104–112.
  • van Assema DME, Lubberink M, Bauer M, et al. Blood-brain barrier P-glycoprotein function in Alzheimer’s disease. Brain. 2012;135:181–189.
  • Deo AK, Borson S, Link JM, et al. Activity of P-glycoprotein, a β-amyloid transporter at the blood-brain barrier, is compromised in patients with mild Alzheimer disease. J Nucl Med. 2014;55:1106–1111.
  • Mehta DC, Short JL, Hilmer SN, et al. Drug access to the central nervous system in Alzheimer’s disease: preclinical and clinical insights. Pharm Res. 2015;32:819–839.
  • Pan Y, Omori K, Ali I, et al. Increased expression of renal drug transporters in a mouse model of familial Alzheimer’s disease. J Pharm Sci. 2019;108(7):2484–2489.
  • Schubert CC, Boustani M, Callahan CM, et al. Comorbidity profile of dementia patients in primary care: are they sicker? J Am Geriatr Soc. 2006;54:104–109.
  • Zuliani G, Galvani M, Sioulis F, et al. Discharge diagnosis and comorbidity profile in hospitalized older patients with dementia. Int J Geriatr Psychiatry. 2012;27:313–320.
  • Ali I, Guidone D, Nicolazzo JA, et al. Impact of reduced P-glycoprotein function on digoxin concentrations in patients with dementia. Br J Clin Pharmacol. 2019;85(10):2351–2359.
  • Jyrkkä J, Enlund H, Korhonen MJ, et al. Patterns of drug use and factors associated with polypharmacy and excessive polypharmacy in elderly persons: results of the Kuopio 75+ study: a cross-sectional analysis. Drugs Aging. 2009;26(6):493–503.
  • Hilmer SN, Gnjidic D. The effects of polypharmacy in older adults. Clin Pharmacol Ther. 2009;85(1):86–88.
  • Thomsen LA, Winterstein AG, Søndergaard B, et al. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care. Ann Pharmacother. 2007;41(9):1411–1426.
  • Huizer-Pajkos A, Kane AE, Howlett SE, et al. Adverse geriatric outcomes secondary to polypharmacy in a mouse model: the influence of aging. J Gerontol A Biol Sci Med Sci. 2016;71(5):571–577.
  • Hurwitz A, Brady DA, Schaal SE, et al. Gastric acidity in older adults. JAMA. 1997;278(8):659–662.
  • Soenen S, Rayner CK, Horowitz M, et al. Gastric Emptying in the Elderly. Clin Geriatr Med. 2015;31(3):339–353.
  • Bohnert T, Gan LS. Plasma protein binding: from discovery to development. J Pharm Sci. 2013;102(9):2953–2994.
  • Rolan PE. Plasma-protein binding displacement interactions - why are they still regarded as clinically important. Br J Clin Pharmacol. 1994;37(2):125–128.
  • Pasqualetti G, Tognini S, Calsolaro V, et al. Potential drug-drug interactions in Alzheimer patients with behavioral symptoms. Clin Interv Aging. 2015;10:1457–1466.
  • Loboz KK, Shenfield GM. Drug combinations and impaired renal function - the ‘triple whammy’. Br J Clin Pharmacol. 2005;59(2):239–243.
  • Thomas MC. Diuretics, ACE inhibitors and NSAIDs - the triple whammy. Med J Aust. 2000;172(4):184–185.
  • Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol. 2007;21(3):217–230.
  • Gnjidic D, Hilmer SN, Le Couteur DG. High-risk prescribing in older people: more harm than good? Aging Health. 2012;8(4):325–327.
  • Singh S, Hamdy S. Dysphagia in stroke patients. Postgrad Med J. 2006;82(968):383–391.
  • Williams NT. Medication administration through enteral feeding tubes. Am J Health Syst Pharm. 2008;65(24):2347–2357.
  • Jabbar A, McClave SA. Pre-pyloric versus post-pyloric feeding. Clin Nutr. 2005;24(5):719–726.
  • Mundi MS, Patel J, McClave SA, et al. Current perspective for tube feeding in the elderly: from identifying malnutrition to providing of enteral nutrition. Clin Interv Aging. 2018;13:1353–1364.
  • Zhu LL, Zhou Q. Therapeutic concerns when oral medications are administered nasogastrically. J Clin Pharm Ther. 2013;38(4):272–276.
  • Magnuson BL, Clifford TM, Hoskins LA, et al. Enteral nutrition and drug administration, interactions, and complications. Nutr Clin Pract. 2005;20(6):618–624.
  • Silva RME, Portela RDP, Da Costa IFR, et al. Immunosuppressives and enteral feeding tubes: an integrative review. J Clin Pharm Ther. 2020;45(3):408–418.
  • Adamji M, Day AS. An overview of the role of exclusive enteral nutrition for complicated Crohn’s disease. Intest Res. 2019;17(2):171–176.
  • Pearson D, May G, Fick GH, et al. Azathioprine for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2000;(2):CD000067.
  • Sacks GS. Drug-nutrient considerations in patients receiving parenteral and enteral nutrition. Pract Gastroenterol. 2004;28(7):39–49.
  • Australian Medicines H. Australian medicines handbook: AMH. Adelaide, South Australia: AMH; 2020.
  • Koren G, Nordon G, Radinsky K, et al. Clinical pharmacology of old age. Expert Rev Clin Pharmacol. 2019;12(8):749–755.
  • Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65.
  • Schaeffner ES, Ebert N, Delanaye P, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med. 2012;157(7):471–U54.
  • Pottel H, Hoste L, Dubourg L, et al. An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant. 2016;31(5):798–806.
  • Corsonello A, Roller-Wirnsberger R, Wirnsberger G, et al. Clinical implications of estimating glomerular filtration rate with three different equations among older people. Preliminary results of the project “screening for chronic kidney disease among older people across Europe (SCOPE)”. J Clin Med. 2020;9(2):17.
  • Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612.
  • Selistre LD, Rech DL, de Souza V, et al. Diagnostic performance of creatinine-based equations for estimating glomerular filtration rate in adults 65 years and older. JAMA Intern Med. 2019;179(6):796–804.
  • Alshaer IM, Kilbride HS, Stevens PE, et al. External validation of the Berlin equations for estimation of GFR in the elderly. Am J Kidney Dis. 2014;63(5):862–865.
  • Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.