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A Pharmacokinetic Formalism Explicitly Integrating the Patient Drug Compliance

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The adherence phenomenon is now well recognized to seriously compromise drug efficacy. In this paper, we analyze the role of compliance through drug intake history as an integral part of the pharmacokinetic process. Being concerned with what is accessible in medical practice, we develop a stochastic approach to model the drug intake behavior that we combine with a conventional pharmacokinetic model in order to investigate the effect of drug intake history on the pharmacokinetic time-course. For this purpose, we explicitly formalize the plasma concentration variations for the most common administration routes. This analytical approach allows to characterize drug concentration variations directly inherited from patient compliance.

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References

  1. World Health Organization. Adherence to Long-term therapies: Evidence for action. http://www.who.int/chronic_conditions/adherencereport/en/ (2003).

  2. Iskedjian M., Einarson T.R., MacKeigan L.D., Shear N., Addis A., Mittmann N., Ilersich A.L. (2002). Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin. Ther. 24(2):302–316

    Article  PubMed  Google Scholar 

  3. Mu S., Ludden T.M. (2003). Estimation of population harmacokinetic parameters in the presence of non-compliance. JPKPD, 30(1):53–81

    Google Scholar 

  4. Vrijens B., Urquhart J. (2005). Patient adherence to prescribed antimicrobial drug dosing regimens. J. Antimicrob. Chemother. 55:616–627

    Article  PubMed  CAS  Google Scholar 

  5. J. Urquhart. A call for a new discipline. Pharm. Tech. 11(12):617 (Editorial), December (1987).

    Google Scholar 

  6. Vrijens B., Urquhart J. (2005). New findings about patient adherence to prescribed drug dosing regimens: an introduction to pharmionics. Eur. J. Hosp. Pharm. Sci. 11(5):103–106

    Google Scholar 

  7. Gibaldi M., Perrier D. (1982). Pharmacokinetics, 2nd edn. Marcel Dekker, New York, NY

    Google Scholar 

  8. Rowland M., Tozer T.N. (1995). Clinical Pharmacokinetics – Concepts and Applications, 3rd edn. Lea & Febiger, Williams & Wilkins, PA

    Google Scholar 

  9. Advance Analytical Research on Drug Exposure. http://www.aardex.ch/aardex/index.htm.

  10. Vrijens B., Goetghebeur E. (2004). Electronic monitoring of variation in drug intakes can reduce bias and improve precision in pharmacokinetic/pharmacodynamic population studies. Stat. Med. 23:531–544

    Article  PubMed  Google Scholar 

  11. Labaune J.P. (1988). Pharmacocinétique. Masson, Paris

    Google Scholar 

  12. W. A. Ritschel and G. A. Kearns. Handbook of Basic Pharmacokinetics, 6th edn. APHA (1999).

  13. Girard P., Blaschke T.F., Kastrissios H., Sheiner L.B. (1998). A Markov mixed effect regression model for drug compliance. Stat. Med. 17:2313–2333

    Article  PubMed  CAS  Google Scholar 

  14. Meyer U.A., Peck C.C. (1997). The drug holiday pattern of noncompliance in clinical trials: challenge to conventional concepts of drug safety and efficacy. Center for Drug Development Science. Georgetown University, Washington, DC

    Google Scholar 

  15. Ng P.K. (1981). Prediction of multiple-dose blood level curves of drugs administered four times daily at non-uniform dosing intervals. Int. J. Biomed. Comput. 12:217–226

    Article  PubMed  CAS  Google Scholar 

  16. Faed E.M. (1981). Model-independent linear pharm,acokinetic equations for variable dosing regimen. Biopharm Drug Dispos. 2:299–302

    Article  PubMed  CAS  Google Scholar 

  17. Niebergall P.J., Sugita E.T., Schnaare R.L. (1974). Calculation of plasma level versus time profiles for variable dosing regimens. J. Pharm. Sci. 63:100–105

    Article  PubMed  CAS  Google Scholar 

  18. Howell J.R. (1975). Mathematical formulation for nonuniform multiple dosing. J. Pharm. Sci. 64:464–466

    Article  PubMed  CAS  Google Scholar 

  19. J. A. Jacquez. Compartmental Analysis in Biology and Medicine, 3rd edn. Biomedware (1996).

  20. C. E. Petit-jetté, J. Li, J. del Castillo, and F. Nekka. Influence of different feeding behavior scenarios on the pharmacokinetics of feed-administered antibiotics in swine: application to chlortetracycline. Submitted.

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Authors and Affiliations

  1. Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, Québec, H3C3J7, Canada

    Jun Li & Fahima Nekka

  2. Centre de recherches mathématiques, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, Québec, H3C3J7, Canada

    Jun Li & Fahima Nekka

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  1. Jun Li
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  2. Fahima Nekka
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Correspondence to Fahima Nekka.

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Li, J., Nekka, F. A Pharmacokinetic Formalism Explicitly Integrating the Patient Drug Compliance. J Pharmacokinet Pharmacodyn 34, 115–139 (2007). https://doi.org/10.1007/s10928-006-9036-y

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  • DOI: https://doi.org/10.1007/s10928-006-9036-y

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