Comparison of the stability and pharmacokinetics in dogs of modified ciclosporin capsules stored at -20°C and room temperature

Vet Dermatol. 2015 Aug;26(4):228-e50. doi: 10.1111/vde.12222.

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.

Hypothesis/objectives: 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.

Animals: 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 and clinical importance: Placing Atopica(®) capsules in a -20°C freezer for 28 days does not affect stability or absorption in the dog.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsules
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics*
  • Dogs
  • Drug Stability
  • Drug Storage* / methods
  • Female
  • Freezing
  • Male
  • Temperature

Substances

  • Capsules
  • Cyclosporine