Pharmacokinetic Considerations in Geriatric Medication
Journal of Pharmaceutical Research International,
Aging have an impact on the pharmacokinetic and pharmacodynamic characteristics of drugs, resulting in clinically relevant safety and efficacy consequences. There appear to be a rise in gastrointestinal (GI) problems with age, and certain slight variations in the GI tract have been noted. Nevertheless, insufficient studies have been done on the impact of aging on the expression and activity of these GI transporters. Aging is associated with some reduction in first-pass metabolism that might be due to a decrease in liver mass and perfusion. Some medications with considerable first-pass metabolism, can have markedly enhanced bioavailability and, as a consequence bioavailability. Other high clearance (CL) medications have identical bioavailability in both young and old individuals. However, at the other hand, the first-pass activation of some prodrugs, may be slowed or decreased, leading to a reduction in bioavailability. Some drugs may have a low bioavailability when taken orally, benefitted from transdermal administration. There are still no specific age-related liver ailments, routine clinical tests of liver function do not vary substantially with age, the course, and outcome of some liver diseases can be affected by age. The characteristic of high or low extraction of a drug by the liver has been attributed to whether the metabolic clearance (CL) of a drug falls or remains unchanged with age. Reduction in renal function in elderly subjects, particularly glomerular filtration rate, affects the clearance of many drugs such as water-soluble antibiotics and nonsteroidal anti-inflammatory drugs. The therapeutic significance of these declines in renal excretion is governed by the drug's expected toxicity. Many drugs show their effects specially in old age patients in different manner and depend on age related factors. It must take appropriate precautions for administering of different drugs to the old age patients.
How to Cite
Massoud L, Agha HA, Taleb M. Pharmacokinetic and pharmacodynamic changes in elderly people. World journal of pharmaceutical and medical research. 2017;3(11):14-23.
Shenoy P, Harugeri A. Elderly patients' participation in clinical trials. Perspectives in Clinical Research. 2015;6(4):184.
Goldacre MJ. Demography of aging and the epidemiology of gastrointestinal disorders in the elderly. Best. Pract. Res. Clin. Gastroenterol. 2009;23(6):793-804.
Bhutto A, Morley JE. The clinical significance of gastrointestinal changes with aging. Curr. Opin. Clin. Nutr. Metab. Care. 2008;11(5):651-660.
Salles N. Basic mechanisms of the aging gastrointestinal tract. Dig. Dis. 2007;25(2): 112-117.
Orr WC, Chen CL. Aging and neural control of the GI tract: IV. Clinical and physiological aspects of gastrointestinal motility and aging. Am. J. Physiol. Gastrointest. Liver Physiol. 2002;283(6): 1226-1231.
Madsen JL, Graff, J. Effects of aging on gastrointestinal motor function. Age Aging. 2004;33(2):154–159.
Shimamoto C, Hirata I, Hiraike Y Takeuchi N, Nomura T, Katsu K. Evaluation of gastric motor activity in the elderly by electrogastrography and the (13) C-acetate breath test. Gerontology. 2002;48(6):381-386.
Hurwitz A, Brady DA, Schaal SE, Samloff IM, Dedon, J, Ruhl CE. Gastric acidity in older adults. JAMA., 1997;278(8):659-662.
Haruma K, Kamada T, Kawaguchi H, Okamoto S, Yoshihara M, Sumii K, Inoue M, Kishimoto, S, Kajiyama G, Miyoshi A. Effect of age and Helicobacter pylori infection on gastric acid secretion. Gastroenterol. Hepatol. 2000;15(3):277-283.
Iijima K, Ohara S, Koike T, Sekine H, Shimosegawa T. Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender. Scand. J. Gastroenterol., 2004;39(8):709-716.
Ciccocioppo R, Sabatino D, Luinetti A, Rossi OM, Cifone MG, Corazza GR. Small bowel enterocyte apoptosis and proliferation are increased in the elderly. Gerontology. 2002; 48(4):204- 208.
Saltzman JR, Kowdley KV, Perrone G, Russell RM. Changes in small-intestine permeability with aging. J. Am. Geriatr. Soc. 1995;43(2):160-164.
Dobson PD, Lanthaler K, Oliver SG, Kell DB. Implications of the dominant role of transporters in drug uptake by cells. Curr. Top. Med. Chem., 2009;9(2):163-181.
Sugano K, Kansy M, Artursson P, Avdeef A, Bendels S, Di L, et al. Coexistence of passive and carrier-mediated processes in drug transport. Nat. Rev. Drug Discov. 2010;9(8):597- 614.
Dobson PD, Kell DB. Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nat. Rev. Drug Discov. 2008;7(3):205-220.
McLean AJ, Le Couteur DG. Aging biology and geriatric clinical pharmacology. Pharmacol. Rev. 2004;56(2):163-184.
Zeeh J, Platt D. The aging liver: structural and functional changes and their consequences for drug treatment in old age. Gerontology. 2002;48(3):121-127.
Tateishi T, Fujimura A, Shiga T, Ohashi K, Ebihara A. Influence of aging on the oxidative and conjugative metabolism of propranolol. Int. J. Clin. Pharmacol. Res. 1995;15(3):95-101.
Anantharaju A, Feller A, Chedid A. Aging Liver. A review. Gerontology. 2002;48(6):343-353.
Fromm MF, Dilger K, Busse D, Kroemer HK, Eichelbaum M, Klotz U. Gut wall metabolism of verapamil in older people: effects of rifampicin-mediated enzyme induction. Br. J. Clin. Pharmacol. 1998;45(3):247-255.
Dilger K, Hofmann U, Klotz U. Enzyme induction in the elderly: effect of rifampin on the pharmacokinetics and pharmacodynamics of propafenone. Clin. Pharmacol. Ther. 2000;67(5):512- 520.
Davies RO, Gomez HJ, Irvin JD, Walker JF. An overview of the clinical pharmacology of enalapril. Br. J. Clin. Pharmacol. 1984;18(2):215S-229S.
Muriel Villoria C, Pérez-Castejón Garrote JM, Sánchez Magro I, Neira Alvarez M. Effectiveness and safety of transdermal buprenorphine for chronic pain treatment in the elderly: a prospective observational study. Med. Clin (Barc). 2007;128(6):204-210.
Vadivelu N,; Hines RL. Management of chronic pain in the elderly:focus on transdermal buprenorphine. Clin. Interv. Aging. 2008;(3):421-430.
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):459-469.
lmadfa I, Meyer AL. Body composition, changing physiological functions and nutrient requirements of the elderly. Ann. Nutr. Metab. 2008;52(1):2-5.
St-Onge MP, Gallagher D. Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition. 2010;26(2):152-155.
Hanratty CG, McGlinchey P, Johnston GD, Passmore AP. Differential pharmacokinetics of digoxin in elderly patients. Drugs Aging, 2000;17(5):353-362.
Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J. Clin. Invest. 1975;55(2):347-359.
Mörike K, Schwab M, Klotz U. Use of aminoglycosides in elderly patients. Pharmacokinetic and clinical considerations. Drugs Aging. 1997;10(4):259-277.
Butler JM, Begg EJ. Free drug metabolic clearance in elderly people. Clin. Pharmacokinet. 2008; 47(5):297-321.
Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin, Pharmacol, Ther. 2002;71(3):115-121.
Benedetti MS, Whomsley R, Poggesi I, Cawello W, Mathy FX, Delporte, ML et al. Drug metabolism and pharmacokinetics. Drug Metab. Rev. 2009;41(3):344-390.
Endres CJ, Endres MG, Unadkat JD. Interplay of drug metabolism and transport:a real phenomenon or an artifact of the site of measurement? Mol. Pharm. 2009; 6(6):1756-1765.
Zhang L, Zhang Y, Huang SM. Scientific and regulatory perspectives on metabolizing enzyme-transporter interplay and its role in drug interactions: challenges in predicting drug interactions. Mol. Pharm. 2009;6(6):1766-1774.
Wynne H. Drug metabolism and ageing. J. Br. Menopause. Soc., 2005;11(2):51-56.
Warren A, Chaberek S, Ostrowski K, Cogger VC, Hilmer SN, McCuskey RS. Effects of old age on vascular complexity and dispersion of the hepatic sinusoidal network. Microcirculation. 2008;15(3):191-202.
Frith J, Jones D, Newton JL. Chronic liver disease in an ageing population. Age Ageing, 2009;38(1): 11-18.
Herrlinger C, Klotz U. Drug metabolism and drug interactions in the elderly. Best Pract. Res. Clin. Gastroenterol. 2001;15(6):897-918.
Le Couteur DG, McLean AJ. The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis. Clin. Pharmacokinet. 1998;34(5):359-373.
Fu A, Sreekumaran Nair K. Age effect on fibrinogen and albumin synthesis in humans. Am J Physiol. 1998;275:E1023–E1030.
Gunasekera JBL, Lee DR, Jones L, Maskrey VL, Swift CG, Jackson SHD. Does albumin fall with increasing age in the absence of disease? Age Ageing. 1996;25(1):29.
Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther. 2002;71:115–121.
Lumholtz B, Kampmann JJ, Siersbaeck-Nielsen K, Hansen JM. Dose regimen of kanamycin and gentamycin. Acta Med Scand. 1974;196:521–524.
Triggs EJ, Johnson JM, Learoyd B. Absorption and disposition of ampicillin in the elderly. Eur J Clin Pharmacol. 1980;18:195–198.
Somogyi A, Hewson D, Muirhead M, Bochner F. Amiloride disposition in geriatric patients: importance of renal function. Br J Clin Pharmacol. 1990;29:1–8.
Portnoi VA. Digitalis delirium in elderly patients. J Clin Pharmacol. 1979;19:747–750.
Rigby JW, Scott AK, Hawksworth GM, Petrie JC. A comparison of the pharmacokinetics of atenolol, metoprolol, oxprenolol and propranolol in elderly hypertensive and young healthy subjects. Br J Clin Pharmacol. 1985;20:327– 331.
Hewick DS, Newbury P, Hopwood S, Naylor G, Moody J. Age as a factor affecting lithium therapy. Br J Clin Pharmacol. 1977;4:201–205.
Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics of indomethacin in the elderly. Clin Pharmacokinet. 1993;24:428–434.
Ritch AE, Perera WN, Jones CJ. Pharmacokinetics of azapropazone in the elderly. Br J Clin Pharmacol. 1982;14:116–119.
Fliser D, Bischoff I, Hanses A, et al. Renal handling of drugs in the healthy elderly. Creatinine clearance underestimates renal function and pharmacokinetics remain virtually unchanged. Eur J Clin Pharmacol. 1999;55:205–211.
O'Malley K, Crooks J, Duke E, Stevenson IH. Effect of age and sex on drug metabolism. Br Med J. 1971;3:607–609.
Swift CG, Homeida M, Halliwell M, Roberts CJ. Antipyrine disposition and liver size in the elderly. Eur J Clin Pharmacol. 1978;14:149–152.
Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging. 2001;18:837–851.
Hunt CM, Westerkam WR, Stave GM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol. 1992;44:275–283.
Hunt CM, Westerkam WR, Stave GM, Wilson JA. Hepatic cytochrome P-4503A (CYP3A) activity in the elderly. Mech Ageing Dev. 1992;64:189–199.
Wood AJ, Vestal RE, Wilkinson GR, Branch RA, Shand DG. Effect of ageing and cigarette smoking on antipyrine and indocyanine green elimination. Clin Pharmacol Ther. 1979;26:16–20
Cusack B, Kelly JG, Lavan J, Noel J, O'Malley K. Theophylline kinetics in relation to age: the importance of smoking. Br J Clin Pharmacol. 1980;10:109–114.
Salem SA, Rajjayabun P, Shepherd AM, Stevenson IH. Reduced induction of drug metabolism in the elderly. Age Ageing. 1978;7:68–73.
Pearson MW, Roberts CJ. Drug induction of hepatic enzymes in the elderly. Age Ageing. 1984;13:313–316.
Feely J, Pereira L, Guy E, Hockings N. Factors affecting the response to inhibition of drug metabolism by cimetidine – dose–response and sensitivity of elderly and induced subjects. Br J Clin Pharmacol. 1984;17:77–81.
Vestal RE, Cusack BJ, Mercer GD, Dawson GW, Park BK. Aging and drug interactions. I. Effect of cimetidine and smoking on oxidation of theophylline and cortisol in healthy men. J Pharmacol Exp Ther. 1987;241:488–500.
Divoll M, Greenblatt DJ, Abernethy DR, Shader RI. Cimetidine impairs clearance of antipyrine and desmethyldiazepam in the elderly. J Am Geriatr Soc. 1982;30:684–689.
Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther. 1980;215:86–91.
Greenblatt DJ, Harmatz JS, Shader RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part I) Clin Pharmacokinet. 1991;21:165–177.
Miners JO, Penhall R, Robson RA, Birkett DJ. Comparison of paracetamol metabolism in young adult and elderly males. Eur J Clin Pharmacol. 1988;35: 157–160.
Wynne HA, Cope LH, Herd B, Rawlins MD, James OF, Woodhouse KW. The association of age and frailty with paracetamol conjugation in man. Age Ageing. 1990;19:419–424.
Rostami-Hodjegan A, Kroemer HK, Tucker GT. In vivo indices of enzyme activity. the effect of renal impairment on the assessment of CYP2D6 activity. Pharmacogenetics. 1999;9:277–286.
Yuan R, Venitz J. Effect of chronic renal failure on the disposition of highly hepatically metabolized drugs. Int J Clin Pharmacol Ther. 2000;38:245–253.
Pichette V, Leblond FA. Drug metabolism in chronic renal failure. Curr Drug Metab. 2003;4:91–103.
Shaojun Shi, Ulrich Klotz. Age-Related Changes in Pharmacokinetics, Current Drug Metabolism, 2011;12:601-610.
Blechman MB, Gelb AM. Aging and gastrointestinal physiology. Clin Geriatr Med. 1999;15:429–38.
Bhantumnavin K, Schuster MM. Ageing and gastrointestinal function. In Handbook of the Biology of Ageing, eds Finch CE, Hayflick L. New York, Van Nostrand Reinhold. 1977;709–23.
Klawans HL. Emerging strategies in Parkinson’s disease. Neurology. 1990; 40(3):1–76.
Vestal RE, McGuire EA, Tobin JD, Andres R, Norris AH, Mezey E.Aging and ethanol metabolism. Clin Pharmacol Ther 1977;21:343–54.
Redolfi A, Borgogelli E, Lodola E. Blood level of cimetidine in relation to age. Eur J Clin Pharmacol 1979;15:257–61.
Cusack B, Kelly J, O’Malley K, Noel J, Lavan J, Horgan J. Digoxinin the elderly: pharmacokinetic consequences of old age. Clin Pharmacol Ther. 1979;25:772–6.
Owen JA, Sitar DS, Berger L, Bronwell L, Duke PC, Mitenko PA.Age-related morphine kinetics. Clin Pharmacol Ther 1983;34:364–8.
Christensen JH, Andreasen F, Jansen JA. Influence of age and sex on the pharmacokinetics of thiopentone. Br J Anaesth. 1981;53:1189–95.
Greenblatt DJ, Allen MD, Harmatz JS, Shuder RI. Diazepam disposition determinants. Clin Pharmacol Ther 1980; 27:301–12.
Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, Wilkinson GR. Effects of ageing and liver disease on disposition of lorazepam. Clin Pharmacol Ther. 1978;24:411–19.
Roberts RK, Wilkinson GR, Branch RA, Schenker S. Effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide (Librium). Gastroen-terology. 1978;75:479–85.
Lumholtz B, Kampmann JJ, Siersbaeck-Nielsen K, Hansen JM. Dose regimen of kanamycin and gentamycin. Acta Med Scand 1974;196:521–4.
Triggs EJ, Johnson JM, Learoyd B. Absorption and disposition of ampicillin in the elderly. Eur J Clin Pharmacol. 1980;18:195–8.
Somogyi A, Hewson D, Muirhead M, Bochner F. Amiloride disposition in geriatric patients: importance of renal function.Br J Clin Pharmacol 1990;29:1–8.
Portnoi VA. Digitalis delirium in elderly patients. J Clin Pharmacol. 1979;19:747–50.
Rigby JW, Scott AK, Hawksworth GM, Petrie JC. A comparison ofthe pharmacokinetics of atenolol, metoprolol, oxprenolol andpropranolol in elderly hypertensive and young healthy subjects. Br J Clin Pharmacol. 1985;20:327–31.
Hewick DS, Newbury P, Hopwood S, Naylor G, Moody J. Age as a factor affecting lithium therapy. Br J Clin Pharmacol. 1977;4:201–5.
Oberbauer R, Krivanek P, Turnheim K. Pharmacokinetics of indomethacin in the elderly. Clin Pharmacokinet. 1993;24:428–34.
Ritch AE, Perera WN, Jones CJ. Pharmacokinetics of azapropazone in the elderly. Br J Clin Pharmacol 1982;14:116–19.
Fliser D, Bischoff I, Hanses A, et al. Renal handling of drugs inthe healthy elderly. Creatinine clearance underestimates renal function and pharmacokinetics remain virtually unchanged. Eur J Clin Pharmacol. 1999;55:205–11.
O’Malley K, Crooks J, Duke E, Stevenson IH. Effect of age and sex on drug metabolism. Br Med J 1971;3:607– 9.
Swift CG, Homeida M, Halliwell M, Roberts CJ. Antipyrine disposition and liver size in the elderly. Eur J Clin Pharmacol. 1978;14:149–52.
Robertson DR, Waller DG, Renwick AG, George CF. Age-related changes in the pharmacokinetics and pharmacodynamics of nifedipine. Br J Clin Pharmacol. 1988;25:297–305.
Castleden CM, George CF. The effect of ageing on the hepatic clearance of propranolol. Br J Clin Pharmacol 1979;7:49–54.
Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI. Sensitivity to triazolam in the elderly. N Engl J Med. 1991;324:1691–8.
Davies RO, Gomez HJ, Irvin JD, Walker JF. An overview of the clinical pharmacology of enalapril. Br J Clin Pharmacol 1984;18(2):215S–229S.
Abstract View: 0 times
PDF Download: 0 times