Skip to main content
SpringerLink
Log in

Drug distribution in the elderly

  • Chapter
Drugs and the Elderly

Abstract

The physicochemical properties of a drug predetermine its basic pattern of distribution within the body after administration. In general, lipophilic drugs will pass across membranes easily, will accumulate in lipid tissues and will be extensively distributed, whereas polar compounds will be restricted to the extracellular fluids and will not transfer into tissues readily. These basic principles were first discussed by Brodie and his co-workers in the early 1950s (for review, see Brodie, 1964) and later by Bender (1969). More recently, Klotz (1976) has emphasised that ‘distribution is a physicochemical interaction between a drug and the body’ and that ‘the pattern of this distribution is determined by the properties of the two partners’.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ball, A. P., Viswan, A. K., Mitchard, M. and Wise, R. (1977). Delayed excretion and prolonged elimination half life of mecillinam in the elderly. J. Antimicrob. Chemother. (in press)

    Google Scholar 

  • Bender, A. D. (1965). The effect of increasing age on the distribution of peripheral flow in man. J. Am. Geriat. Soc. 13, 192–98

    Article  Google Scholar 

  • Bender, A. D. (1969). Geriatric pharmacology; age and its influence on drug action in adults. Drug Information Bull, 3, 153–58

    Google Scholar 

  • Bender, A. D., Post, A., Meier, J. P., Higson, J. E. and Reichard, G. (1975). Plasma protein binding of drugs as a function of age in adult human subjects. J. pharm. Sci., 64, 1711–13

    Article  Google Scholar 

  • Brandfonbrener, A. D., Landowne, M. and Shock, N. W. (1955). Changes in cardiac output binding of drugs as a function of age in adult human subjects. J. pharm. Sci., 64, 1711–13

    Google Scholar 

  • Brandfonbrener, A. D., Landowne, M. and Shock, N. W. (1955). Changes in cardiac output with age. Circulation, 12, 557–66

    Article  Google Scholar 

  • Brodie, B. B. (1964). Physico-chemical Factors in Drug Absorption and Distribution of Drugs (ed. T. B. Binns) Livingstone, Edinburgh and London, p. 16

    Google Scholar 

  • Chan K., Kendall, M J. and Mitchard, M. (1974). The effect of age on plasma pethidine levels. Clin. Sci. mol. Med, 47, 23 p

    Google Scholar 

  • Chan, K., Kendall, M. J., Mitchard, M., Wells, W. D. E. and Vickers, M. D. (1975). The effect of age on plasma pethidine concentrations. Br. J. clin. Pharmac, 2, 297–302

    Article  Google Scholar 

  • Dodge, J. T., Mitchell, C. and Hanahan, D. J. (1963). The preparation and chemical characteristics of haemoglobin-free ghosts of human erythrocytes. Arch Biochem. Biophys, 100, 119

    Article  Google Scholar 

  • Edelman, L. S. and Leibman, J. (1959). Anatomy of body water and electrolytes. Am. J. Med., 27, 256–77

    Article  Google Scholar 

  • Evans, G. H., Nies, A. S. and Shand, D. G. (1973). The disposition of propranolol. III Decreased half-life and volume of distribution as a result of plasma binding in man, monkey, dog and rat. J. Pharmac. exp. Ther., 186, 114–22

    Google Scholar 

  • Evans, G. H. and Shand, D. G. (1973). Disposition of propranolol. VI Independent variation in steady state circulating drug concentrations and half-life as a result of plasma drug binding in man. Clin. Pharmac. Ther., 14, 499–500

    Google Scholar 

  • Ewy, G. A., Kapadia, G. G., Yao, L., Luillin M. and Marcus, F. I. (1969). Digoxin metabolism in the elderly. Circulation, 39, 449–53

    Article  Google Scholar 

  • Forbes, G. B. and Reina, J. C. (1970). Adult lean body mass declines with age: some longitudinal observations. Metabolism, 19, 653–63

    Article  Google Scholar 

  • Goldman, R. (1971). Decline in organ function with ageing. In Clinical Geriatrics (ed. I. Rossman), Lippincott, Philadelphia

    Google Scholar 

  • Gomperts, E. D., Cantrell, A. C. and Zail, S. S. (1971). Electrophoretic patterns of red-cell membrane protein from various mammalian species. Br. J. Hae. mat, 21, 429–32

    Article  Google Scholar 

  • Gregerman, R. I., Gaffney, G. W. and Shock. N. W. (1962). Thyroxine turnover in euthyroid man with special reference to changes with age. J. clin. Invest, 41, 2065–74

    Article  Google Scholar 

  • Hayes M. J., Langman, M. J. S. and Short, A. H. (1975a). Changes in drug metabolism with increasing age. 1. Warfarin binding and plasma proteins. Br. J. clin. Pharmac, 2, 69–72

    Article  Google Scholar 

  • Hayes, M. J., Langman, M. J. S. and Short, A. H. (1975b). Changes in drug metabolism with increasing age. Phenytoin clearance and protein binding. Br. J. clin. Pharmac, 2, 73–79

    Article  Google Scholar 

  • Hooper W. D., Bochner, F, Eodie, M. J. and Tyner, J. H. (1974). Plasma protein binding of diphenylhydantoin: effects of sex hormones, renal and hepatic disease. Clin. Pharmac. Ther 15. 276–82

    Google Scholar 

  • Jusko, W. J. and Gretch, M. (1977). Plasma and tissue protein binding of drugs in pharmacokinetics. Drug Metabolism Rev, 5, 43–140

    Article  Google Scholar 

  • Klotz, U. (1976). Pathophysiological and disease-induced changes in drug distribution volume: pharmacokinetic implications. Clin. Pharmacokin, 1, 204–18

    Article  Google Scholar 

  • Klotz, U., Avant, G. R., Hayumpa, A., Schenker, S. and Wilkinson, G. R. (1975). The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J. clin. Invest, 55, 347–59

    Article  Google Scholar 

  • Leask, R. G. S., Andrew, G. R. and Caird, F I. (1973). Normal values for sixteen blood constituents in the elderly. Age and Ageing, 2, 14–23

    Article  Google Scholar 

  • Maddy, A. H. (1966). The properties of the protein of the plasma membrane of ox erythrocytes. Biochim. Biophys. Acta, 117, 193–95

    Article  Google Scholar 

  • Mather, L. E., Tucker, G. T., Pflug A. E., Lindop, M. J. and Wilkerson, C. (1975). Meperidine kinetics in man; intravenous injection in surgical patients and volunteers. Clin. Pharmac. Ther, 17, 21–30

    Google Scholar 

  • Moore, R. G., Triggs, E. J., Shanks, C. A. and Thomas, J. (1975). Pharmacokinetics of chemothiazole in humans. Eur. J. Clin. Pharmac, 8, 353–57

    Article  Google Scholar 

  • Nation, R. L., Learoyd, B., Barber, J. and Triggs, E. J. (1976). The pharmacokinetics of chlormethiazole following intravenous administration in the elderly. Eur. J. clin. Pharmacol, 10, 407–15

    Article  Google Scholar 

  • Novak, L. P. (1972). Ageing, total body potassium, fat free mass and cell mass in males and females between the ages 18 and 85 years. J. Gerontol, 27, 438–43

    Article  Google Scholar 

  • O’Malley, K., Crooks. J. Duke, E. and Stevenson, I. H. (1971). Effect of age and sex on human drug metabolism. Br. med. J. 3, 607–9

    Article  Google Scholar 

  • Perrier, D. and Gibaldi, M. (1973). Relationship between plasma or serum drug concentration and amount of drug in the body at steady state upon multiple dosing. I Pharmacokin. Biopharm, 1, 17–22

    Article  Google Scholar 

  • Riegelman, S., Loo. J. C. K. and Rowland, M. (1968). Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. pharm. Sci., 57, 117–23

    Article  Google Scholar 

  • Rosenberg, S. A. and Guidotti, G. (1968). The protein of human erythrocyte membranes. J. biol. Chem, 243, 1985

    Google Scholar 

  • Rowland, M., Benet, L. Z. and Graham, G. G. (1973). Clearance concepts in pharmacokinetics. J. Pharmacokin. Biopharm, 1, 123–36

    Article  Google Scholar 

  • Shepherd, A. M. M., Hewick, D. S., Moreland, T. S. and Stevenson, I. H. (1977). Age as a determinant of sensitivity to warfarin. Br. J. clin. Pharmac, 4, 315–20

    Article  Google Scholar 

  • Sherlock, S., Bearn, A. G., Billing, B. H. and Paterson, J. C. S. (1950). Splanchnic blood flow in man by the bromsulfalein method: the relation of peripheral plasma bromsulfalein level to the calculated flow. J lab. clin. Med. 35, 923–32

    Google Scholar 

  • Simon, C., Malerczyk, V., Müller, U. and Müller, G. (1972). Zur Pharmakokinetik von Pro-picillin bei geriatrischen Patienten im Vergleich zu jungeren Erwachsenen. D. Med. Wschr., 97, 1999–2003

    Article  Google Scholar 

  • Triggs, E. J., Nation, R. L., Long, A. and Ashley, J. J. (1975). Pharmacokinetics in the elderly. Eur. J. clin. Pharmac, 8, 55–62

    Article  Google Scholar 

  • Vinuela E., Algratini, I. D. and Ochoa, S. (1967). Synthesis of virus specific proteins in Escherichia coli infected with the RNA bacteriophage MS2. Eur. J. Biochem, 1, 1

    Article  Google Scholar 

  • Wallace, S., Whiting, B. and Runcie, J (1976). Factors affecting drug binding in plasma of elderly patients. Br. J. clin. Pharmac., 3, 327–30

    Article  Google Scholar 

  • Wilkinson, G. R. (1975). Pharmacokinetics of drug disposition: hemodynamic considerations. A. Rev. Pharmac, 15, 11–27

    Article  Google Scholar 

  • Wilkinson, G. R. and Kurata, D. (1974). The uptake of diphenylhydantoin by the human erythrocyte and its application to the estimation of plasma binding. In Drug Interactions (ed. C. Morselli, S. Garattini and S. Cohen), Raven Press, New York

    Google Scholar 

  • Woodford-Williams, E., Alvares, A. S., Webster, D., Lardless, B. and Dixon, M. P. (1964). Serum protein patterns in ‘normal’ and pathological ageing. Gerontologia, 10, 86–99

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Pharmacokinetic Group, Department of Medical Research, Synthélabo — L.E.R.S, 75013, Paris, France

    M. Mitchard

Authors
  1. M. Mitchard
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, Ninewells Hospital, Dundee, UK

    J. Crooks  & I. H. Stevenson  & 

Copyright information

© 1979 J. Crooks and I. H. Stevenson

About this chapter

Cite this chapter

Mitchard, M. (1979). Drug distribution in the elderly. In: Crooks, J., Stevenson, I.H. (eds) Drugs and the Elderly. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-03813-8_7

Download citation

Publish with us

Policies and ethics

Search

Navigation