A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models

J Neurosci Methods. 2014 Dec 30:238:105-11. doi: 10.1016/j.jneumeth.2014.09.019. Epub 2014 Sep 26.


Background: Nonadherence to a physician-prescribed therapeutic intervention is a costly, dangerous, and sometimes fatal concern in healthcare. To date, the study of nonadherence has been constrained to clinical studies. The novel approach described herein allows for the preclinical study of nonadherence in etiologically relevant disease animal model systems.

New method: The method herein describes a novel computer-automated pellet delivery system which allows for the study of nonadherence in animals. This system described herein allows for tight experimenter control of treatment using a drug-in-food protocol. Food-restricted animals receive either medicated or unmedicated pellets, designed to mimic either "taking" or "missing" a drug.

Results: The system described permits the distribution of medicated or unmedicated food pellets on an experimenter-defined feeding schedule. The flexibility of this system permits the delivery of drug according to the known pharmacokinetics of investigational drugs.

Comparison with other methods: Current clinical adherence research relies on medication-event monitoring system (MEMS) tracking caps, which allows clinicians to directly monitor patient adherence. However, correlating the effects of nonadherence to efficacy still relies on the accuracy of patient journals.

Conclusion: This system allows for the design of studies to address the impact of nonadherence in an etiologically relevant animal model. Given methodological and ethical concerns of designing clinical studies of nonadherence, animal studies are critical to better understand medication adherence. While the system described was designed to measure the impact of nonadherence on seizure control, it is clear that the utility of this system extends beyond epilepsy to include other disease states.

Keywords: Anti-seizure drug; Chronic drug delivery; Drug discovery; Epilepsy; Nonadherence; Noncompliance.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics
  • Carbamazepine / administration & dosage
  • Carbamazepine / pharmacokinetics
  • Computers
  • Disease Models, Animal*
  • Drug Delivery Systems / instrumentation*
  • Drug Delivery Systems / methods*
  • Electrical Equipment and Supplies
  • Epilepsy / drug therapy
  • Equipment Design
  • Food Dispensers, Automatic / instrumentation*
  • Infrared Rays
  • Internet
  • Medication Adherence*
  • Software*


  • Anticonvulsants
  • Carbamazepine