Effects of Oral Single-Dose Empagliflozin on Urinary Glucose, Serum β-Hydroxybutyrate, and Plasma Empagliflozin Concentrations in Healthy Adult Dogs.

Empagliflozin is a sodium-glucose cotransporter-2 inhibitor used for treating humans with heart failure, among other conditions. This drug could have applications in veterinary cardiology, but whether empagliflozin has biological effects in dogs when administered at dosages approximating human therapeutic dosages is unknown. This study investigated whether empagliflozin (target dosage, 0.3 mg/kg) could produce significant increases in urinary glucose concentrations and measurable plasma drug concentrations, without increasing serum β-hydroxybutyrate (β-HA) concentrations in dogs. Six healthy, privately-owned dogs weighing 22-36 kg were studied prospectively. Urinary glucose, serum β-HA, and plasma empagliflozin concentrations were measured 0 h, 6 h, 12 h, 24 h, 48 h, and 72 h after single-dose oral administration of 10 mg empagliflozin. The dosage administered was 0.28-0.45 mg/kg. Mean urinary glucose concentration peaked at 24 h (8,041 mg/dL) before returning to baseline (< 40 mg/dL) at 72 h (p < 0.001). Serum β-HA concentrations remained within the reference interval for dogs (< 2.1 mg/dL). Plasma drug concentrations at 24 h were 13 times greater than the reported human in vitro IC50. The half-life was 4.4-6 h. Oral empagliflozin 0.28-0.45 mg/kg produced glucosuria and measurable plasma drug concentrations in healthy dogs, without ketonemia, after a single dose.