title: Comparison of the stability and pharmacokinetics in dogs of modified ciclosporin capsules stored at -20°C and room temperature.
abstract: BACKGROUND
  Placement of ciclosporin (Atopica(®); Novartis Animal Health, Greensboro, NC, USA) capsules in a freezer prior to administration may reduce the incidence of vomiting in dogs. However, its impact on ciclosporin stability and pharmacokinetics is unknown.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the stability of Atopica(®) capsules and pharmacokinetics of ciclosporin in dogs after storage at -20°C in comparison with storage of capsules at 15-25°C. We hypothesized that there would be no difference in stability or pharmacokinetic parameters between freezer-stored and room-temperature Atopica(®) capsules.
  
  
  METHODS
  Eight healthy research beagle dogs received one 5.0 mg/kg oral dose each of freezer-stored and room-temperature Atopica(®) capsules with a 1 week washout period between.
  
  
  METHODS
  Ciclosporin concentrations of all available Atopica(®) capsule strengths were assessed for stability after -20°C storage at five time points over 30 days and at room temperature (15-25°C). A blinded, randomized cross-over study was also performed to compare blood concentrations of ciclosporin after capsule storage for 28 days at -20 versus 15-25°C. Blood samples were obtained over a 24 h period after administration. Capsule and whole-blood ciclosporin concentrations were assessed via high-performance liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  There was no significant difference in stability between freezer-stored and room-temperature Atopica(®) capsules at any time point. In the cross-over study, there were no significant differences in pharmacokinetic parameters assessed.
  
  
  CONCLUSIONS
  Placing Atopica(®) capsules in a -20°C freezer for 28 days does not affect stability or absorption in the dog.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
authors.forename: Jeremy C
authors.identifier: http://orcid.org/0000-0002-0648-7900
authors.initials: JC
authors.lastname: Bachtel
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pendergraft
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
authors.forename: Rodney A W
authors.initials: RA
authors.lastname: Rosychuk
authors.affiliation: Pharmacology Core, University of Colorado Comprehensive Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gustafson
authors.affiliation: Pharmacology Core, University of Colorado Comprehensive Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hansen
authors.affiliation: Pharmacology Core, University of Colorado Comprehensive Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lunghofer
mesh_terms: D000818:Animals; D002214:Capsules; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D005260:Female; D005615:Freezing; D008297:Male; D013696:Temperature
chemical_list: D002214:Capsules; D016572:Cyclosporine