Jeremy C Bachtel1, Jennifer S Pendergraft1, Rodney A W Rosychuk1, Daniel L Gustafson2, Ryan J Hansen2, Paul J Lunghofer2. 1. Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA. 2. Pharmacology Core, University of Colorado Comprehensive Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80525, USA.
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.
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.
Authors: Anuradha Krishnamurthy; Arvind Dasari; Anne M Noonan; Janice M Mehnert; Albert C Lockhart; Stephen Leong; Anna Capasso; Mark N Stein; Hanna K Sanoff; James J Lee; Aaron Hansen; Usha Malhotra; Sarah Rippke; Daniel L Gustafson; Todd M Pitts; Kim Ellison; S Lindsey Davis; Wells A Messersmith; S Gail Eckhardt; Christopher H Lieu Journal: Cancer Res Date: 2018-07-24 Impact factor: 12.701