Resident CSU Small Animal Internal Medicine Fort Collins, CO, United States
Abstract: Background. Prednisolone is used in treating immune-mediated disease (IMD) and lymphoma (LSA) in dogs. The impact of these two diseases on the pharmacokinetic and pharmacodynamic (PK/PD) parameters of prednisolone in dogs has not been previously investigated. Hypothesis/Objectives. We hypothesized that prednisolone PK parameters would exhibit dose dependence in both diseases, and the impact on modulating immune responses would be greatest in dogs with IMD. Objective 1: Determine prednisolone pharmacokinetics at doses of 1 mg/kg and 2 mg/kg in dogs with IMD and LSA. Objective 2. Assess prednisolone effects on immune transcriptomes and cytokines. Animals. Dogs with IMD (n = 10) or lymphoma (n = 10) were enrolled to determine prednisolone PK/PD parameters at doses of 1 mg/kg/day and 2 mg/kg/day. Methods. Prednisolone concentrations were determined using standard methodology, leukocyte transcriptome analysis was performed using a Nanostring platform, and plasma cytokines were done by multiplex assay. Results. Prednisolone concentrations exhibited minimal dose-dependence in dogs with IMD. There was evidence of decreased absorption in the 1mg/kg LSA group. Transcriptome analysis of circulating leukocytes revealed suppression of the G2M checkpoint and IFN-α in IMD dogs, and suppression of IFN-α in LSA dogs. Conclusions and clinical importance. Both PK and PD parameters associated with oral prednisolone administration were significantly affected by disease status in dogs. The immune modifying activity of prednisolone was also different between dogs with IMD and lymphoma. We conclude that disease status can impact prednisolone absorption in dogs with IMD or LSA.
