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. 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.