title: A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bioengineering Dept, University of Utah, Salt Lake City, UT, USA.
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Thomson
authors.affiliation: Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA. Electronic address: steve.white@hsc.utah.edu.
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics; D002220:Carbamazepine / Q000008:administration & dosage / Q000493:pharmacokinetics; D003201:Computers; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D055615:Electrical Equipment and Supplies; D004827:Epilepsy / Q000188:drug therapy; D004867:Equipment Design; D005509:Food Dispensers, Automatic / Q000295:instrumentation*; D007259:Infrared Rays; D020407:Internet; D055118:Medication Adherence; D012984:Software
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine
keywords: Anti-seizure drug; Chronic drug delivery; Drug discovery; Epilepsy; Nonadherence; Noncompliance