Skip to main content
SpringerLink
Log in

Relevance of the Application of Pharmacokinetic-Pharmacodynamic Modelling Concepts in Drug Development

The ‘Wooden Shoe’ Paradigm

  • Leading Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Van Boxtel CJ, Holford NHG, Danhof M. The in vivo study of drug action: concepts and applications of kinetic-dynamic modelling. Amsterdam: Elsevier Science Publishers, 1992

    Google Scholar 

  2. Derendorf H, Hochhaus G. Handbook of pharmacokinetic/ pharmacodynamic correlation. Boca Raton: CRC Press, 1995

    Google Scholar 

  3. Yacobi A, Skelly JP, Shah VP, et al. Integration of pharmacokinetics, pharmacodynamics and toxicokinetics in rational drug development. New York: Plenum Press, 1993

    Google Scholar 

  4. Rowland M, Aarons L, editors. New strategies in drug development and clinical evaluation: the population approach. Luxembourg: Office for Offical Publications of the European Communities, 1992

    Google Scholar 

  5. Sheiner LB, Stanski DR, Vozeh S, et al. Simultaneous modelling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther 1979; 25: 358–71

    PubMed  CAS  Google Scholar 

  6. Fuseau E, Sheiner LB. Simultaneous modeling of pharmacokinetics and pharmacodynamics with a nonparametric pharmacodynamic model. Clin Pharmacol Ther 1984; 35: 733–41

    Article  PubMed  CAS  Google Scholar 

  7. Unadkat J, Bartha F, Sheiner LB. Simultaneous modelling of pharmacokinetics and pharmacodynamics with nonparamet-ric kinetic and dynamic models. Clin Pharmacol Ther 1986; 40: 86–93

    Article  PubMed  CAS  Google Scholar 

  8. Veng-Pedersen P, Mandema JW, Danhof M. A system approach to pharmacodynamics III: an algorithm and computer program ‘COLAPS’ for pharmacodynamic modeling. J Pharm Sci 1991; 80: 86–93

    Google Scholar 

  9. Veng-Pedersen P, Modi NB. Pharmacodynamic system analysis of the biophase level predictor and the transduction function. J Pharm Sci 1992; 81: 925–34

    Article  PubMed  CAS  Google Scholar 

  10. Dayneka NL, Garg V, Jusko WJ. Comparison of four basic models of indirect pharmacodynamic responses. J Pharmacokinet Biopharm 1993; 21: 457–78

    PubMed  CAS  Google Scholar 

  11. Jusko WJ, Ko HC. Physiologic indirect response models characterize diverse types of pharmacodynamic effects. Clin Pharmacol Ther 1994; 56: 406–19

    Article  PubMed  CAS  Google Scholar 

  12. Dingemanse J, Danhof M, Breimer DD. Pharmacokinetic-pharmacodynamic modelling of CNS drug effects. Pharmacol Ther 1988; 38: 1–52

    Article  PubMed  CAS  Google Scholar 

  13. Blue JW, Colburn WA. Efficacy measures: surrogates or clinical outcomes? J Clin Pharmacol 1996; 36: 767–70

    PubMed  CAS  Google Scholar 

  14. Peck CC, Barr WH, Benet LZ, et al. Opportunities for integration of pharmacokinetics, pharmacodynamics and toxicokinetics in rational drug development. Clin Pharmacol Ther 1992 Apr; 51: 465–73

    Article  PubMed  CAS  Google Scholar 

  15. Lieberman R, McMichael J. Role of pharmacokinetic-pharmacodynamic principles in rational and cost-effective drug development. Ther Drug Monit 1996; 18: 423–8

    Article  PubMed  CAS  Google Scholar 

  16. Danhof M, Mandema JW, Hoogerkamp A, et al. Pharmacokinetic-pharmacodynamic modelling in pre-clinical investigations: principles and perspectives. Eur J Drug Metab Pharmacokinet 1993; 18: 41–7

    Article  PubMed  CAS  Google Scholar 

  17. Nagashima R, O’Reilly R, Levy G. Kinetics of pharmacologic effects in man: the anticoagulant action of warfarin. Clin Pharmacol Ther 1969; 10: 22–35

    PubMed  CAS  Google Scholar 

  18. Yacobi A, Wingard LB, Levy G. Comparative pharmacokinetics of coumarin anticoagulants X: relationship between distribution, elimination and anticoagulant action of warfarin. J Pharm Sci 1974; 63: 868–72

    Article  PubMed  CAS  Google Scholar 

  19. Mandema JW, Tukker E, Danhof M. In vivo characterization of the pharmacodynamic interaction of a benzodiazepine agonist and antagonist: midazolam and flumazenil. J Pharmacol Exp Ther 1992; 260: 36–44

    PubMed  CAS  Google Scholar 

  20. Breimer LTM, Burm AGL, Danhof M, et al. Pharmacokineticpharmacodynamic modelling of the interaction between flumazenil and midazolam in volunteers by aperiodic EEG analysis. Clin Pharmacokinet 1991; 20: 497–508

    Article  PubMed  CAS  Google Scholar 

  21. Struyker Boudier HAJ, Van Essen H, Smits JFM. Can reflex increase in heart rate and cardiac output of arteriolar vasodilators in hypertension be avoided? [abstract no. 429]. First European Meeting on Hypertension; 1983 May 24-Jun 1: Milan

  22. Kleinbloesem CH, Van Brummelen P, Danhof M, et al. Rate of increase in the plasma concentration of nifedipine as a major determinant of its hemodynamic effects in humans. Clin Pharmacol Ther 1987; 41: 20–30

    Article  Google Scholar 

  23. Urquhart J. Role of patient compliance in clinical pharmacokinetics: review of recent research. Clin Pharmacokinet 1994; 27: 202–15

    Article  PubMed  CAS  Google Scholar 

  24. Mandema JW, Sansom LN, Dios-Vieitez MC, et al. Pharmacokinetic-pharmacodynamic modelling of the EEG effect of benzodiazepines: correlation with receptor binding and anti-convulsant activity. J Pharmacol Exp Ther 1991; 257: 472–8

    PubMed  CAS  Google Scholar 

  25. Mandema JW, Kuck MT, Danhof M. Differences in intrinsic efficacy of benzodiazepines are reflected in their concentration EEG effect relationship. Br J Pharmacol 1992; 105: 164–70

    Article  PubMed  CAS  Google Scholar 

  26. Mathôt RAA, Van den Aarsen BCFM, Soudijn W, et al. Pharmacokinetic-pharmacodynamic modelling of the cardiovascular effects of R-and S-H6 phenylisopropyl-adenosine in conscious normotensive rats. J Pharmacol Exp Ther 1995; 273: 405–14

    PubMed  Google Scholar 

  27. Levy G. The case for preclinical pharmacodynamics. In: Yacobi A, Skelly JP, Shah VP, et al., editors. Integration of pharmacokinetics, pharmacodynamics and toxicokinetics in rational drug development. New York: Plenum Press, 1993: 7–13

    Google Scholar 

  28. Collins JM. Use of pharmacokinetics and pharmacodynamics in preclinical studies to guide dosage escalation schemes in phase I studies of anticancer drugs. In: Yacobi A, Skelly JP, Shah VP, et al., editors. Integration of pharmacokinetics, pharmacodynamics and toxicokinetics in rational drug development. New York: Plenum Press, 1993: 49–54

    Google Scholar 

  29. Egan TD, Minto CF, Hermann DJ, et al. Remifentanil versus alfentanil: comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology 1996; 84: 821–33

    Article  PubMed  CAS  Google Scholar 

  30. Van Steveninck AL, Verver S, Schoemaker RC, et al. Effects of temazepam on saccadic eye movements: concentration-effect relationships in individual healthy volunteers. Clin Pharmacol Ther 1992; 52; 402–8

    Article  PubMed  Google Scholar 

  31. Kleinbloesem CH, Van Brummelen P, Van Harten J, et al. Nifedipine: influence of renal function on pharmacokinetic/ haemodynamic relationship. Clin Pharmacol Ther 1985; 37: 563–74

    Article  PubMed  CAS  Google Scholar 

  32. Kleinbloesem CH, Van Harten J, Wilson JHP, et al. Nifedipine: kinetics and dynamics in patients with liver cirrhosis after intravenous and oral administration. Clin Pharmacol Ther 1986; 40: 21–8

    Article  PubMed  CAS  Google Scholar 

  33. Peck CC. How golden are the eggs? Inaugural lecture held on the occasion of the Boerhaave Professorship at Leiden University, The Netherlands, 1994

  34. Sheiner LB. The intellectual health of clinical drug evaluation. Clin Pharmacol Ther 1991; 50; 409

    Article  Google Scholar 

  35. Steimer JL, Kawai, R, Charnick S, et al. Physiological pharmacokinetic/pharmacodynamic (PB-PK/PD) models in drug development? Proceedings of the 2nd International Symposium on Measurement and Kinetics of In Vivo Drug Effects; 1994 Apr 14–16; Noordwijkerhout, The Netherlands. Leiden: Leiden/Amsterdam Center for Drug Research, 1994

Download references

Author information

Authors and Affiliations

  1. Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Sylvius Laboratories, P.O. Box 9503, 2300 RA, Leiden, The Netherlands

    Douwe D. Breimer & Meindert Danhof

Authors
  1. Douwe D. Breimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meindert Danhof
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Breimer, D.D., Danhof, M. Relevance of the Application of Pharmacokinetic-Pharmacodynamic Modelling Concepts in Drug Development. Clin-Pharmacokinet 32, 259–267 (1997). https://doi.org/10.2165/00003088-199732040-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199732040-00001

Keywords

Search

Navigation