graduated student Azabu University Sagamihara, Kanagawa, Japan
Abstract:
Background: Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor used in the treatment of human patients with heart failure. Despite its potential applications in veterinary medicine, no studies have evaluated its pharmacodynamics in dogs. Hypothesis/
Objectives: To evaluate the dose-dependent effects of single dosing of dapagliflozin on pharmacodynamics, diuresis and ketogenesis in dogs. Animals: Five clinically healthy dogs.
Methods: Each dog received all treatments (single oral dose of dapagliflozin at 0.1, 0.3, or 1.0 mg/kg, and placebo) in a randomized sequence, with a 14-day washout period between each treatment. Urine and blood samples were collected at predefined time points (0, 1, 2, 3, 4, 5, 6, 9, 12, and 24 hours post-administration) to evaluate urine volume; plasma glucose, ketone bodies, and electrolytes (sodium, chloride, and potassium); and urine glucose and electrolytes.
Results: 24-hour urinary glucose excretion was significantly increased in the 0.3 mg/kg group compared to the 0.1 mg/kg group (P = .02). However, no significant difference in 24-hour urinary glucose excretion was observed between 0.3 mg/kg and 1.0 mg/kg groups. Plasma ketone body concentration was significantly higher in the 1.0 mg/kg group compaired to the placebo group at 4, 5, 6, 12, and 24 hours post-administration (P < .05). No significant differences were observed among the four groups (placebo, 0.1 mg/kg, 0.3 mg/kg, and 1.0 mg/kg) in urine volume; plasma glucose and electrolytes; and urinary electrolytes. Conclusions and Clinical importance: Single oral dose dapagliflozin increased urinary glucose excretion with a dose-dependent increase observed up to 0.3 mg/kg, and induced ketogenesis in dogs.
