Evaluation of dose-dependent effects of dapagliflozin on urinary glucose and plasma ketone bodies in healthy dogs

Objective: To evaluate the dose-dependent effects of single dosing of dapagliflozin on pharmacodynamics, diuresis, and ketogenesis in dogs. Methods: This study included 5 healthy Beagles. A single dose of dapagliflozin (0.1, 0.3, or 1.0 mg/kg) or placebo was orally administered (randomized 14-day intervals) to each dog. Blood and urine samples were collected prior to administration and at 1, 2, 3, 4, 5, 6, 9, 12, and 24 hours after administration. A urinary catheter was placed from 0 to 6 hours after administration to monitor urine volume and collect samples; thereafter, urine was collected using a metabolic cage. Plasma ketone bodies, sodium, potassium, chloride, and glucose concentrations were measured. Urinary sodium, potassium, chloride, glucose, and urine volume were measured and compared among the treatment groups. Results: 24-hour urinary glucose excretion was significantly increased in the 0.3-mg/kg group compared with the 0.1-mg/kg group. However, no significant difference in 24-hour urinary glucose excretion was observed between the 0.3-and 1.0-mg/kg groups. Plasma ketone body concentration was significantly higher in the 1.0-mg/kg group compared with the placebo group at 4, 5, 6, 12, and 24 hours after administration. The 6-hour urine volume (mL/kg) was significantly higher in the 1.0-mg/kg group compared with the placebo group. Conclusions: In healthy dogs, a single oral administration of dapagliflozin at 1.0 mg/kg induced both ketogenic and diuretic effects. Clinical Relevance: This study provides preliminary insight into dapagliflozin's effects in healthy dogs; further studies are needed to assess relevance in dogs with heart failure.