Determination of absolute bioavailability, absorption, metabolism, and excretion of evogliptin in healthy male subjects using a microtracer method.

Evogliptin, a selective serine protease dipeptidyl peptidase-4 inhibitor, has been approved in Korea for the treatment of type 2 diabetes. In this study, we investigated the absorption, metabolism, and excretion of evogliptin in healthy male subjects. To determine the extent of absolute oral bioavailability (F), one group of six participants received a microtracer intravenous (IV) dose, a 10-min infusion of 20 µg [¹⁴C]-evogliptin (651 nCi) commencing 4 h after administration of a 5 mg oral evogliptin tablet. A second group of six participants received an oral solution of [¹⁴C]-evogliptin (5 mg: 1000 nCi) to determine pharmacokinetics, mass balance recovery, plasma and excreta metabolite profiles, and structural identification of metabolites. The F of the 5 mg evogliptin tablet was 50.2%. Evogliptin exhibited a long elimination half-life of 40-55 h after both the IV and oral doses. Following oral administration of [¹⁴C]-evogliptin, more than 75.3% of the dose was absorbed. An average of 88.9% of the total radioactivity (TRA) dose was recovered in excreta over 240 h, with 46.1% via urine and 42.8% via feces. Evogliptin was metabolised through oxidation to M7 and M8, sulfation to M13, and subsequent glucuronide conjugation of M7 to M16. No single metabolite accounted for more than 10% of the TRA in plasma. The concomitant oral dosing followed by microtracer IV dosing and the microtracer oral dosing enabled a comprehensive description of evogliptin's absorption, metabolism, and excretion in humans. Evogliptin was safe and well tolerated in healthy subjects.