THE IMPACT OF PATIENT COMPLIANCE ON DRUG CONCENTRATION PROFILE IN MULTIPLE DOSES

Physicians commonly prescribe drugs in a multiple dosage regimen for p rolonged therapeutic activity. To study the effect of multiple dosing on drug concentration in blood, researchers often use deterministic mo dels with the assumption that drugs are administered at a fixed dosage , with equal or unequal (fixed) dosing intervals. In practice, many pa tients do not comply with such a rigid schedule. Hence, two possible s cenarios might occur: patients might not take the prescribed dosing am ount, resulting in erratic dosing sizes; they might not adhere to the dosing schedule, resulting in erratic dosing times. We propose separat e statistical models for these two scenarios and study their impact on blood serum/plasma concentration. With non-compliance, some basic con cepts such as steady state need new definition. We provide a rigorous formulation for the principle of superposition which enables us to gen eralize the concept of steady state. Applying the proposed models, we demonstrate that non-compliance causes the drug concentration time cur ve to exhibit an increase in fluctuation. The increase in fluctuation due to non-compliance cannot be explained with use of the classical de terministic multiple dose model.