title: Long-acting atypical antipsychotics: characterization of the local tissue response.
abstract: OBJECTIVE
  Long-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation in the tissue, which has not been well defined in the literature. The purpose of this work is to establish an experimental baseline for describing these responses.
  
  
  METHODS
  Non-human primates and rodents were used to examine the response to LAI formulations of two clinically relevant atypical antipsychotics, aripiprazole monohydrate and olanzapine pamoate monohydrate.
  
  
  RESULTS
  A foreign body response develops with elevations of key cytokines such as IL-1α, IL-1β, TNFα, and IL6 at the site of injection. However, the tissue response for the two atypical antipsychotics compounds diverge as evidenced by quantitative differences observed in cytokine levels at various time points after dosing.
  
  
  CONCLUSIONS
  Our studies show that, while the drugs are in the same therapeutic class, the response to each of these compounds can be distinguished qualitatively and quantitatively, supporting the idea that the injection site reaction involves a multiplicity of factors including the properties of the compound and cellular dynamics at the site of injection.
authors.affiliation: Alkermes, Inc., 852 Winter Street, Waltham, Massachusetts, 02451, USA, sara.paquette@alkermes.com.
authors.forename: Sara Montminy
authors.initials: SM
authors.lastname: Paquette
authors.forename: Had
authors.initials: H
authors.lastname: Dawit
authors.forename: Magali B
authors.initials: MB
authors.lastname: Hickey
authors.forename: Elaine
authors.initials: E
authors.lastname: Merisko-Liversidge
authors.forename: Orn
authors.initials: O
authors.lastname: Almarsson
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Deaver
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000378:metabolism*; D000068180:Aripiprazole; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008297:Male; D010879:Piperazines / Q000008:administration & dosage* / Q000378:metabolism*; D015363:Quinolones / Q000008:administration & dosage* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D018836:Inflammation Mediators; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole