Pharmacokinetics of Bexagliflozin After Intravenous and Oral Administration in Cats

Abstract

Bexagliflozin, a selective sodium–glucose cotransporter 2 (SGLT2) inhibitor, has been developed for feline diabetes mellitus. This study characterized bexagliflozin pharmacokinetics in healthy cats after single intravenous and oral administrations. Sixteen adult cats received a 1 mg/kg intravenous solution and a 15 mg oral tablet (Bexacat) in a two-period study under fasted conditions. Serial plasma samples were collected up to 72 h and analyzed by a validated LC–MS/MS method (calibration range 1–2000 ng/mL). Pharmacokinetic parameters were derived by non-compartmental analysis. Following intravenous dosing, bexagliflozin showed a low plasma clearance of 348 mL/h/kg. The volumes of distribution during the terminal phase (V_z) and at steady-state (V_SS) were 3.5 and 1.7 L/kg, respectively. The terminal half-life was 7.0 h. After oral dosing of the tablet, absorption was rapid (median T_max 1 h; range 0.5–4 h), with C_max of 1780 ng/mL and a terminal half-life of 6.9 h. Absolute bioavailability was 78% (90% confidence interval: 73%–83%). Exposure was comparable between males and females after both routes (AUC ratios ~97%–103%). Treatments were well tolerated. These pharmacokinetic data indicate bexagliflozin exhibits rapid absorption, high oral bioavailability, and a half-life compatible with once-daily dosing in cats.