What Additional Information Can we Retrieve When Compliance is Accounted For? An explicit Compliance-Pharmacokinetic Formalism
F. Nekka, J. Li and F. Fenneteau
Universite de Montreal
Objectives: Compliance reflects the patient drug input and has to be considered as a history of drug intake. Quality of compliance should be judged through its impact on drug therapy. As such, the compliance phenomenon has to be explicitly formalized and properly characterized in terms of fate of drugs. Having this in mind, we assessed the effect of compliance and extracted its main characteristics.
Methods: We formalized the notion of randomness in drug intake behavior and explicitly included it into a pharmacokinetic model to characterize its effect on the concentration variation. For this, we adopted a stochastic approach to model non-compliance behavior using a general distribution which can be accessible by recording patient drug history
Results: We proved that the stochastic feature of drug intake, previously treated as a nonsystematic noise to a deterministic model, is in fact an inherent component which has to be considered as a part of the mechanistic model. Indeed, in the case of poor compliance, we can retract the source of what is generally classified as pure noise. Thus, the variable compliance behavior adds additional variation to the regular oscillation curve that we have properly characterized.
Conclusions: The benefit of this approach is evident since the knowledge of the origin of the variation will allow an objective intervention. We have developed a general formalism of the compliance phenomenon that can be adapted to different situations, i.e., different compliance patterns in various pathologies.
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 J. Li and F. Nekka, A Pharmacokinetic Formalism Explicitly Integrating the Patient Drug Compliance, Journal of Pharmacokinetics and Pharmacodynamics, vol. 34, no. 1, pp. 115-139, 2007.