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• W2066562457 abstract "KR-66223 is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that is under development for the treatment of type 2 diabetes. We studied the pharmacokinetic and pharmacodynamic characteristics of KR-66223 in rats, monkeys, and dogs to predict PK/PD profiles in humans. KR-66223 exhibited a moderate volume of distribution (0.3-1.8L/kg), moderate systemic clearance (1-1.76L/h/kg), long half-life (> 3h), and low oral bioavailability (below 2.5% in all tested species). The EC50s for DPP-4 inhibition as calculated by the Emax model was below 4.25 ng/mL across all species, confirming KR-66223 as a potent DPP-4 inhibitor. In vitro plasma protein binding suggested that it was available (69-89%), correlating with its volume of distribution in animals. Using allometric scaling and the Emax model, human systemic clearance, volume of the central compartment, volume of the peripheral compartment, and EC50 for DPP-4 inhibition were predicted to be 0.31 L/h/kg, 0.1 L/kg, 2.4L/kg, and 3ng/mL, respectively. These results can serve as a valuable foundation for future clinical trials." @default.
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• W2066562457 date "2012-01-01" @default.
• W2066562457 modified "2023-09-27" @default.
• W2066562457 title "Pharmacokinetics and Pharmacodynamics of KR-66223 a Novel DPP-4 Inhibitor" @default.
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• W2066562457 doi "https://doi.org/10.2133/dmpk.dmpk-11-rg-095" @default.
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