Pharmacokinetic Changes in the Elderly

Celil İlker AŞKINa , Gökçe Sevim ÖZTÜRK FİNCANa

aGazi University Faculty of Medicine, Department of Medical Pharmacology, Ankara, Türkiye

ABSTRACT
In elderly patients, concurrent diseases can occur, therefore the elderly require more prescriptions. The term pharmacokinetics refers to what the body does to the medicine, and it covers four primary areas which are absorption, distribution, metabolism, and elimination. Deterioration due to old age in physiological functions causes changes in pharmacokinetic parameters in the elderly. Due to reduced gastric acid production, gastric motility, and blood flow, absorption can be altered in older patients. Alterations in body composition such as decline in body water levels and increase in body fat levels affect the distribution of drugs. With aging, liver mass and hepatic blood flow decreases, in return, clearance of substances that are metabolized in the liver decreases. With aging kidney function is affected therefore drug clearance is altered. When treating elderly patients, approaching with caution can be advised since these changes can be dangerous due to possible toxicities or unfavorable treatment outcomes.
Keywords: Pharmacokinetics; aging

Referanslar

  1. OECD. "Elderly population" (indicator). [cited: 9 August 2023]. [Crossref]
  2. Jaul E, Barron J. Age-Related Diseases and Clinical and Public Health Implications for the 85 Years Old and Over Population. Front Public Health. 2017;5:335. [Crossref]  [PubMed]  [PMC]
  3. Centers for Disease Control and Prevention (CDC) (Internet), 2013 [cited: 2023 August]. Health, United States, 2013: with special features on prescription drugs. Access link: [Link]
  4. Pizzuti R, Caffari B, Binkin N; Gruppo ARGENTO. La prescrizione di farmaci nell'anziano: risultati dello studio Argento [Prescription drugs and the elderly: results of the Argento study]. Ig Sanita Pubbl. 2006;62(1):11-26. Italian.
  5. Watts G. Why the exclusion of older people from clinical research must stop. BMJ. 2012;344:e3445. [Crossref]  [PubMed]
  6. Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 12. Baskı. Ankara: Feryal Matbaacılık San. Ve Tic. Ltd. Şti.; 2009.
  7. Corsonello A, Onder G, Maggio M, Corica F, Lattanzio F. Medications affecting functional status in older persons. Curr Pharm Des. 2014;20(19):3256-63. [Crossref]  [PubMed]
  8. Stader F, Siccardi M, Battegay M, Kinvig H, Penny MA, Marzolini C. 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. [Crossref]  [PubMed]
  9. Percival RS, Challacombe SJ, Marsh PD. Flow rates of resting whole and stimulated parotid saliva in relation to age and gender. J Dent Res. 1994;73(8):1416-20. [Crossref]  [PubMed]
  10. Smith CH, Boland B, Daureeawoo Y, Donaldson E, Small K, Tuomainen J. Effect of aging on stimulated salivary flow in adults. J Am Geriatr Soc. 2013;61(5):805-8. [Crossref]  [PubMed]
  11. Noble RE. Drug therapy in the elderly. Metabolism. 2003;52(10 Suppl 2):27-30. [Crossref]  [PubMed]
  12. Khan MS, Roberts MS. Challenges and innovations of drug delivery in older age. Adv Drug Deliv Rev. 2018;135:3-38. [Crossref]  [PubMed]
  13. Baron JH. Studies of basal and peak acid output with an augmented histamine test. Gut. 1963;4(2):136-44. [Crossref]  [PubMed]  [PMC]
  14. Benson JM. Antimicrobial Pharmacokinetics and Pharmacodynamics in Older Adults. Infect Dis Clin North Am. 2017;31(4):609-17. [Crossref]  [PubMed]
  15. Evans MA, Triggs EJ, Cheung M, Broe GA, Creasey H. Gastric emptying rate in the elderly: implications for drug therapy. J Am Geriatr Soc. 1981;29(5):201-5. [Crossref]  [PubMed]
  16. Stader F, Kinvig H, Penny MA, Battegay M, Siccardi M, Marzolini C. Physiologically Based Pharmacokinetic Modelling to Identify Pharmacokinetic Parameters Driving Drug Exposure Changes in the Elderly. Clin Pharmacokinet. 2020;59(3):383-401. [Crossref]  [PubMed]
  17. Perrie Y, Badhan RK, Kirby DJ, Lowry D, Mohammed AR, Ouyang D. The impact of ageing on the barriers to drug delivery. J Control Release. 2012;161(2):389-98. [Crossref]  [PubMed]
  18. Bender AD. The Effect of Increasing Age on the Distribution of Peripheral Blood Flow in Man. J Am Geriatr Soc. 1965;13:192-8. [Crossref]  [PubMed]
  19. Warren PM, Pepperman MA, Montgomery RD. Age changes in small-intestinal mucosa. Lancet. 1978;2(8094):849-50. [Crossref]  [PubMed]
  20. Davis SS, Hardy JG, Fara JW. Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986;27(8):886-92. [Crossref]  [PubMed]  [PMC]
  21. Uluoğlu C. Geriatrik Psikofarmakoloji: Farmakokinetik ve Farmakodinamik Faktörler Açısından İlaç Yanıtı. Turkiye Klinikleri Psychiatry Special Topics. 2010;3(1):47-59.
  22. Hilmer SN. ADME-tox issues for the elderly. Expert Opin Drug Metab Toxicol. 2008;4(10):1321-31. [Crossref]  [PubMed]
  23. Ramsay SE, Whincup PH, Shaper AG, Wannamethee SG. The relations of body composition and adiposity measures to ill health and physical disability in elderly men. Am J Epidemiol. 2006;164(5):459-69. [Crossref]  [PubMed]
  24. ElDesoky ES. Pharmacokinetic-pharmacodynamic crisis in the elderly. Am J Ther. 2007;14(5):488-98. [Crossref]
  25. Hanratty CG, McGlinchey P, Johnston GD, Passmore AP. Differential pharmacokinetics of digoxin in elderly patients. Drugs Aging. 2000;17(5):353-62. [Crossref]  [PubMed]
  26. McLean AJ, Le Couteur DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev. 2004;56(2):163-84. [Crossref]  [PubMed]
  27. Le Couteur DG, McLean AJ. The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet. 1998;34(5):359-73. [Crossref]  [PubMed]
  28. Paxton JW, Briant RH. Alpha 1-acid glycoprotein concentrations and propranolol binding in elderly patients with acute illness. Br J Clin Pharmacol. 1984;18(5):806-10. [Crossref]  [PubMed]  [PMC]
  29. Wallace S, Whiting B. Factors affecting drug binding in plasma of elderly patients. Br J Clin Pharmacol. 1976;3(2):327-30. [Crossref]  [PubMed]  [PMC]
  30. Tumer N, Scarpace PJ, Lowenthal DT. Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol. 1992;32:271-302. [Crossref]  [PubMed]
  31. Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol Aging. 2009;30(3):337-52. [Crossref]  [PubMed]
  32. Waade RB, Molden E, Refsum H, Hermann M. Serum concentrations of antidepressants in the elderly. Ther Drug Monit. 2012;34(1):25-30. [Crossref]  [PubMed]
  33. Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging. 2001;18(11):837-51. [Crossref]  [PubMed]
  34. Parkinson A, Mudra DR, Johnson C, Dwyer A, Carroll KM. The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol Appl Pharmacol. 2004;199(3):193-209. [Crossref]  [PubMed]
  35. Dorne JL, Walton K, Slob W, Renwick AG. Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate?. Food Chem Toxicol. 2002;40(11):1633-56. [Crossref]  [PubMed]
  36. Polasek TM, Patel F, Jensen BP, Sorich MJ, Wiese MD, Doogue MP. Predicted metabolic drug clearance with increasing adult age. Br J Clin Pharmacol. 2013;75(4):1019-28. [Crossref]  [PubMed]  [PMC]
  37. Tillmann J, Reich A. Psychopharmacology and pharmacokinetics. Handb Clin Neurol. 2019;167:37-56. [Crossref]  [PubMed]
  38. Tierney J. Practical issues in geriatric psychopharmacology. J Indian Med Assoc. 1999; 97(4):145-7.
  39. Bennett WM. Geriatric pharmacokinetics and the kidney. Am J Kidney Dis. 1990;16(4):283-8. [Crossref]  [PubMed]
  40. Stahlmann R, Lode H. Safety considerations of fluoroquinolones in the elderly: an update. Drugs Aging. 2010;27(3):193-209. [Crossref]  [PubMed]
  41. Hurria A, Blanchard MS, Synold TW, Mortimer J, Chung CT, Luu T, et al. Age-related changes in nanoparticle albumin-bound paclitaxel pharmacokinetics and pharmacodynamics: influence of chronological versus functional age. Oncologist. 2015;20(1):37-44. [Crossref]  [PubMed]  [PMC]
  42. Reuben DB, Rubenstein LV, Hirsch SH, Hays RD. Value of functional status as a predictor of mortality: results of a prospective study. Am J Med. 1992;93(6):663-9. Erratum in: Am J Med 1993;94(2):232. Erratum in: Am J Med 1993;94(5):560. [Crossref]  [PubMed]
  43. Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: A review. Eur J Intern Med. 2016;31:3-10. [Crossref]  [PubMed]
  44. Hogan DB, Maxwell CJ, Afilalo J, Arora RC, Bagshaw SM, Basran J, et al. A Scoping Review of Frailty and Acute Care in Middle-Aged and Older Individuals with Recommendations for Future Research. Can Geriatr J. 2017;20(1):22-37. [Crossref]  [PubMed]  [PMC]
  45. Hubbard RE, O'Mahony MS, Woodhouse KW. Medication prescribing in frail older people. Eur J Clin Pharmacol. 2013;69(3):319-26. [Crossref]  [PubMed]
  46. Vass M, Hendriksen C. Medication for older people-aspects of rational therapy from the general practitioner's point of view. Z Gerontol Geriatr. 2005;38(3):190-5. [Crossref]  [PubMed]