22-PUB: Pharmacokinetics of RDSY1801 Enteric-Coated Capsules after Oral Administration in Dogs

Introduction and Objective: RDSY1801 enteric-coated capsules effectively reduced postprandial hyperglycemia and HbA1c in diabetic dogs. This study was to evaluate the oral pharmacokinetics of RDSY1801 enteric-coated capsules in beagle dogs. Methods: The pharmacokinetics of RDSY1801 were investigated in beagle dogs after intravenous, subcutaneous and oral administration. Plasma concentrations of RDSY1801 were analyzed using LC-MS/MS, and the pharmacokinetic parameters (Mean±SD) were generated using a non-compartmental model with WinNonlin software. Results: The pharmacokinetics of RDSY1801 after intravenous injection (30 μg/kg, n=10) showed the mean Tmax of 0.083±0.001 hours, T1/2 of 0.076±0.028 hours, and Cmax of 103.68±14.30 ng/ml and AUCinf of 30.5±4.98 ng/ml*h, indicating the low volume of distribution and high clearance. The pharmacokinetics of RDSY1801 after subcutaneous injection (12 μg/kg) showed the mean Tmax of 0.83±0.26 hours, T1/2 of 0.94±0.55 hours, Cmax of 7.30±2.16 ng/ml, and the bioavailability was 86.36%. The oral pharmacokinetics of RDSY1801 enteric-coated capsules (1.2, 3, 12, 24, and 60 mg/dog, respectively) showed that Cmax was consistently achieved at about 3 hours (Tmax), and the Cmax and AUC increased linearly with escalating doses. The Cmax and AUC values ​​of male dogs were higher than those of female dogs at the same dose, and the calculated oral bioavailabilities were 2.62±0.52% in male dogs and 1.57±0.51% in female dogs. Conclusion: RDSY1801 was able to enter the systemic circulation after an oral administration of RDSY1801 enteric-coated capsules although its oral bioavailability was low. Disclosure W. Jin: Employee; Current; Landing Laboratories. J. Wang: Employee; Current; Landing Laboratories. B. Zhang: Employee; Current; Landing Laboratories. X. Liu: Employee; Current; Landing Laboratories. Y. Chen: None. Y. Liu: Employee; Current; RxD Nova Pharmaceuticals, Inc. W. Shen: None.