Skip to main content

Advertisement

SpringerLink
Log in

Compliance spectrum as a drug fingerprint of drug intake and drug disposition

  • Original Paper
  • Published:
Journal of Pharmacokinetics and Pharmacodynamics Aims and scope Submit manuscript

Abstract

Since drug related variability arises from different origins, particularly driven by the behaviour or physiology of the patient, the problems of drug intake and drug disposition are separately presented in general. To overcome the potential drawbacks of this artificial split, we propose in this paper a combined illustrative approach, named compliance spectrum, such that these two subprocesses can be equitably studied and visualized. We construct the compliance spectrum based on the Bayesian decision method we previously developed for the inverse problem of patient compliance within the framework of Population-PK. This spectrum provides an intuitive and interactive way to evaluate the relationship between drug intake and drug disposition along with their consequences on PK profile. As well, it opens a new direction for model quality diagnostic.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. World Health Organization (2003) Adherence to long-term therapies: evidence for action, http://www.who.int/chp/knowledge/publications/adherence_report/en/

  2. Harter JG, Peck CC (1991) Chronobiology suggestions for integrating it into drug development, Ann N Y Acad Sci 618:563–571

    Article  PubMed  CAS  Google Scholar 

  3. Urquhart J (2000) Erratic patient compliance with prescribed drug regimens: target for drug. Clin Pharmacol Ther 67(4):331–334

    Article  PubMed  CAS  Google Scholar 

  4. Macilwain Colin (1997) Better adherence vital in AIDS therapies. Nature 390:326

    Article  PubMed  Google Scholar 

  5. Blaschke TF, Osterberg L, Vrijens B, Urquhart J (2012) Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annu Rev Pharmacol Toxicol 52:275–301

    Article  PubMed  CAS  Google Scholar 

  6. Kenna LA, Sheiner LB (2004) Estimating treatment effect in the presence of non-compliance measured with error: precision and robustness of data analysis methods. Stat Med 23(23):3561–80

    Article  PubMed  Google Scholar 

  7. Mu S, Ludden TM (2003) Estimation of population pharmacokinetic parameters in the presence of non-compliance. J Pharmacokinet Pharmacodyn 30(1):53–81

    Article  PubMed  Google Scholar 

  8. Vrijens B, Tousset E, Rode R, Bertz R, Mayer S, Urquhart J (2005) Successful projection of the time course of drug concentration in plasma during a 1-Year period from electronically compiled dosing-time data used as input to individually parameterized pharmacokinetic models. J Clin Pharmacol 45:461

    Article  PubMed  CAS  Google Scholar 

  9. Vrijens B, Goetghebeur E, de Klerk E, Rode R, Mayer S, Urquhart J (2005) Modelling the association between adherence and viral load in HIV-infected patients. Stat Med 24:2719–2731

    Article  PubMed  Google Scholar 

  10. Girard P, Blaschke TF, Kastrissios H et al. (1998) A Markov mixed effect regression model for drug compliance. Stat Med 17:2313–2333

    Article  PubMed  CAS  Google Scholar 

  11. Wang W, Husan F, Chow S (1996) The impact of patient compliance on drug concentration profile in multiple doses. Stat Med 15(6):659–669

    Article  PubMed  CAS  Google Scholar 

  12. Li J, Nekka F (2007) A pharmacokinetic formalism explicitly integrating the patient drug compliance. J Pharmacokinet Pharmacodyn 34(1):115–39

    Article  PubMed  Google Scholar 

  13. Li J, Nekka F (2009) A probabilistic approach for the evaluation of pharmacological effect induced by patient irregular drug intake. J Pharmacokinet Pharmacodyn 36(3):221–46

    Article  PubMed  Google Scholar 

  14. Sarem S, Li J, Nekka F (2011) Compliance descriptors: analysis and evaluation in terms of therapeutic effect. Biopharm Drug Dispos 32(2):76–88

    Article  PubMed  CAS  Google Scholar 

  15. Barriére O, Li J, Nekka F (2011) A Bayesian approach for the estimation of patient compliance based on the last sampling information. J pharmacokinet pharmacodyn 38(3):333–51

    Article  PubMed  Google Scholar 

  16. Rubio A, Cox C, Weintraub M (1992) Prediction of diltiazem plasma concentration curves from limited measurements using compliance data. Clin pharmacokinet 22(3):238–246

    Article  PubMed  CAS  Google Scholar 

  17. Widmer N, Decosterd LA, Csajka C, Leyvraz S, Duchosal MA, Rosselet A, Rochat B, Eap CB, Henry H, Biollaz J, Buclin T (2006) Population pharmacokinetics of imatinib and the role of alpha-acid glycoprotein. Br J Clin Pharmacol 62(1):97–112

    Article  PubMed  CAS  Google Scholar 

  18. Feng Y, Gastonguay MR, Pollock BG, Frank E, Kepple GH, Bies RR (2011) Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy. Neuropsychiatr Dis Treat 7:117–25

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work has been supported by Mprime, FQRNT and NSERC. The Centre de Recherches Mathématiques and Faculty of Pharmacy of Université de Montréal are also acknowledged for their support. Special thanks for Professor Alain Arnéodo for his valuable comments and suggestions.

Author information

Authors and Affiliations

  1. Faculté de Pharmacie, Université de Montréal C.P. 6128, Succ. Centre-ville, Montréal, QC, H3C 3J7, Canada

    Olivier Barrière, Jun Li & Fahima Nekka

  2. Centre de recherches mathématiques, Université de Montréal C.P. 6128, Succ. Centre-ville, Montréal, QC, H3C 3J7, Canada

    Jun Li & Fahima Nekka

  3. Centre for Applied Mathematics in Bioscience and Medicine, McGill University 3655 Promenade Sir William Osler, Montréal, QC, H3G 1Y6, Canada

    Olivier Barrière, Jun Li & Fahima Nekka

Authors
  1. Olivier Barrière
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fahima Nekka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fahima Nekka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrière, O., Li, J. & Nekka, F. Compliance spectrum as a drug fingerprint of drug intake and drug disposition. J Pharmacokinet Pharmacodyn 40, 41–52 (2013). https://doi.org/10.1007/s10928-012-9285-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10928-012-9285-x

Keywords

Search

Navigation