Skip to main content
Log in

Pharmacokinetics — Uses and abuses

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

It is apparent from studying recent articles on pharmacokinetics that a number of misunder-standings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Agoston, S., Vermeer, G.A., Kersten, U.W., Meijer, D.K.F.: The fate of pancuronium bromide in man. Acta anaesth. Scand.17 267–275 (1973)

    Google Scholar 

  2. Brodie, B.B.: Symposium on clinical drug evaluation and human pharmacology. VI. Difficulties in extrapolating data on metabolism of drugs from animal to man. Clin. Pharmacol. Ther.3 374–380 (1962)

    Google Scholar 

  3. Coltart, D.J., Shand, D.G.: Plasma propranolol levels in the quantitative assessment ofβ-adrenergic blockade in man. Brit. med. J.1970 III 731–734

    Google Scholar 

  4. Enna, S.J., Shanker, L.S.: Absorption of drugs from the rat lung. Amer. J. Physiol.223 1227–1231 (1972)

    Google Scholar 

  5. Fell, P.J.: The compartmental analysis of cortisol and synthetic steroid blood levels; results in health and disease. M.D. thesis, University of London 1973

  6. Fell, P.J., Quantock, D.C., van Lierop, T.HM.T.: Methodologies in drug assessment using computer techniques. In: International aspects of drug evaluation and usage, pp. 155–169. (eds. Jouhar, A.J., Grayson, M.F.) Edinburgh, London: Churchill Livingstone 1973

    Google Scholar 

  7. Gibaldi, M., Levy, G., Weintraub, H.: Drug distribution and pharmacologic effects. Clin. Pharmacol. Ther.12 734–742 (1971)

    Google Scholar 

  8. Glass, H.I., de Garreta, A.C.: Quantitative analysis of exponential curve fitting for biological applications. Phys. in Med. Biol.12 379–388 (1967)

    Google Scholar 

  9. Levy, G., Hollister, L.E.: Variation in rate of salicylate elimination by humans. Brit. med. J.1964 II 286–288

    Google Scholar 

  10. Marquardt, D.W.: An algorithm for least-squares estimation of nonlinear parameters. J. Soc. incl. appl. Math.11 431–441 (1963)

    Google Scholar 

  11. Mortimer, P.R., Mackie, D.B., Haynes, S.: Ampicillin levels in human bile in the presence of biliary tract disease. Brit. med. J.1969 III 88–89

    Google Scholar 

  12. Myhill, J.: Investigation of the effect of data error in the analysis of biological tracer data. Biophys. J.7 903–911 (1967)

    Google Scholar 

  13. Nelson, E.: Kinetics of drug absorption, distribution, metabolism, and excretion. J. pharm. Sci.50 181–192 (1961)

    Google Scholar 

  14. Paterson, J.W., Connolly, J.W., Dollery, C.T., Hayes, A., Cooper, R.G.: The pharmacodynamics of propranolol in man. Pharmacol. Clin.2 127–133 (1970)

    Google Scholar 

  15. Perl, W., Rackow, H., Salanitre, E., Epstein, R.M., Wolf, C.L.: Intertissue diffusion effect of inert fat soluble gases. J. appl. Physiol.20 621–627 (1965)

    Google Scholar 

  16. Riegelman, S., Loo, J.C.K., Rowland, M.: Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. pharm. Sci.57 117–123 (1968)

    Google Scholar 

  17. Riggs, D.S.: The mathematical approach to physiological problems. Baltimore: Williams & Wilkins 1963

    Google Scholar 

  18. Rolinson, G.N., Batchelor, F.R.: Penicillin metabolites. Antimicrob. Ag. Chemother. 654–660 (1962)

  19. Rolinson, G.N., Sutherland, R.: The binding of antibiotics to serum proteins. Br. J. Pharmacol.25 638–650 (1965)

    Google Scholar 

  20. Turner, P.: Blood level or pharmacological response? Brit. J. Clin. Pharmacol.1 11 (1974)

    Google Scholar 

  21. Wagner, J.G.: Some possible errors in the plotting and interpretation of semilogarithmic plots of blood level and urinary excretion data. J. pharm. Sci.52 1097–1101 (1963)

    Google Scholar 

  22. Wagner, J.G.: Pharmacokinetics. Ann. Rev. Pharmacol.8 67–94, (1968)

    Google Scholar 

  23. Weinges, K.F., Fell, P.J., Ehrhardt, I., Ehrhardt, M.: Kinetics of cortisol in health and liver disease. Acta. endocr. (Kbh.) Suppl.155, 158 (1971)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fell, P.J., Stevens, M.T. Pharmacokinetics — Uses and abuses. Eur J Clin Pharmacol 8, 241–248 (1975). https://doi.org/10.1007/BF00567122

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00567122

Key words

Navigation