Designing drug regimens that mitigate nonadherence
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Publication:2079020
Abstract: Medication adherence is a well-known problem for pharmaceutical treatment of chronic diseases. Understanding how nonadherence affects treatment efficacy is made difficult by the ethics of clinical trials that force patients to skip doses of the medication being tested, the unpredictable timing of missed doses by actual patients, and the many competing variables that can either mitigate or magnify the deleterious effects of nonadherence, such as pharmacokinetic absorption and elimination rates, dosing intervals, dose sizes, adherence rates, etc. In this paper, we formulate and analyze a mathematical model of the drug concentration in an imperfectly adherent patient. Our model takes the form of the standard single compartment pharmacokinetic model with first order absorption and elimination, except that the patient takes medication only at a given proportion of the prescribed dosing times. Doses are missed randomly, and we use stochastic analysis to study the resulting random drug level in the body. We then use our mathematical results to propose principles for designing drug regimens that are robust to nonadherence. In particular, we quantify the resilience of extended release drugs to nonadherence, which is quite significant in some circumstances, and we show the benefit of taking a double dose following a missed dose if the drug absorption or elimination rate is slow compared to the dosing interval. We further use our results to compare some antiepileptic and antipsychotic drug regimens.
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Cited in
(9)- Assessing pharmacokinetic variability directly induced by drug intake behaviour through development of a feeding behaviour-pharmacokinetic model
- Design of incentive programs for optimal medication adherence in the presence of observable consumption
- Variability and singularity arising from poor compliance in a pharmacokinetic model. II: The multi-oral case
- Variability and singularity arising from a piecewise-deterministic Markov process applied to model poor patient compliance in the multi-IV case
- Statistical analysis of two-compartment pharmacokinetic models with drug non-adherence
- Understanding and Quantifying Network Robustness to Stochastic Inputs
- A mathematical model of reward-mediated learning in drug addiction
- How missed doses of antibiotics affect bacteria growth dynamics
- Stochastic chiral pharmacokinetics: dynamics with dual randomized dosing regimens
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