AZD4721 (RIST4721) is the potent and orally active antagonist of acidic CXC chemokine receptor 2 ( CXCR2 ). AZD4721 has the potential for the research of inflammatory disease.

This study evaluates the pharmacokinetic (PK) profile of AZD4721 (RIST4721) in rats and dogs. It provides a comparison of predicted and observed clearance (CL) rates, including hepatic metabolic CL, observed CL, renal CL, and biliary CL, measured in ml/min per kilogram. Additionally, it assesses the in vivo/in vitro unbound CL, steady-state volume distribution (V SS) measured in l/kg, half-life (T 1/2) in hours, and oral bioavailability (F %). The findings reveal differences in the pharmacokinetic behavior between the two species, with noted values in rats being a predicted hepatic metabolic CL of 1.7 and an observed CL of 2.4, while in dogs, these values are 0.80 and 0.50 respectively. Renal and biliary CL were found to be less than 0.01 in rats and slightly higher in dogs. In vivo/in vitro unbound CL, V SS, and T 1/2 also differ, with rats showing a faster metabolism and clearance compared to dogs. The oral bioavailability is 45% in rats and 82% in dogs.