In vivo study | In the oral glucose tolerance test (OGTT) in lean mice, oral administration of Omarigliptin 1 hour before glucose screening significantly and concentration-dependently reduced blood glucose excursions. Administration of omarigliptin concentration-dependently increases the blood concentration of the active GLP-1. Its pharmacokinetic studies in male Sprague-Dawley rats and Beagles showed that omarigliptin has a low clearance rate (0.9 − 1.1 mL/min/kg); the volume of distribution at steady state is 0.8 − 1.3 L/kg; The terminal half-life is long, about 11-22 h. In dogs and rats, the oral bioavailability of omarigliptin is high, almost 100%. During the study, omarigliptin was well tolerated and no significant changes in mortality or physiological parameters were observed. After a single oral dose of 25 mg of omarigliptin in subjects, omarigliptin was rapidly absorbed in vivo, reaching a peak concentration (Cmax) of 750 nmol/L within 1 H. In subjects, the bioavailability was ≥ 74%. |