Evaluating the consistency of pharmacotherapy exposure by use of state-of-the-art techniques

Objective: The authors examine the usefulness of population pharmacokinetics coupled with electronic compliance monitoring in evaluating consistency of exposure to pharmacotherapy. Adherence to pharmacotherapy can have a significant impact on drug response, especially in the treatment of schizophrenia and depression. Previous studies evaluating antipsychotics identified schizophrenic individuals with poor pharmacotherapy adherence as having a higher risk of rehospitalization. Other investigators have shown a relationship between pattern of taking selective serotonin-reuptake inhibitors (SSRIs) and probability of a positive outcome. Therefore, it is important to measure adherence patterns in clinical trials evaluating these treatments and to incorporate this information into the research findings. Methods: Two multisite trials with atypical antipsychotics and antidepressants were simulated to evaluate, by use of population pharmacokinetic methods, the impact of electronic monitoring on measuring consistency of exposure to pharmacotherapy. One of the trials is ongoing and evaluates exposure to atypical antipsychotics, and the other is a proposed trial that examines exposure to an SSRI. Results: Erratic exposure patterns were detected with population pharmacokinetic techniques in the absence of Electronic Medication Event Monitoring (MEMS(TM)) data. In our simulations, the use of electronic monitoring improved the identification of atypical exposure by population pharmacokinetics both for the atypical antipsychotics and SSRIs. Conclusion: Our simulations demonstrate the potential usefulness of the combination of population pharmacokinetics with electronic monitoring as a robust method for accurately and precisely capturing both magnitude and consistency of pharmacotherapy exposure.