Pharmacokinetics of Ilunocitinib, a New Janus Kinase Inhibitor, in Dogs

ABSTRACT Ilunocitinib, a novel Janus kinase inhibitor, is indicated for managing pruritus and skin lesions associated with canine allergic and atopic dermatitis. Pharmacokinetics of ilunocitinib were investigated following single intravenous and oral administrations, both in fed and fasted states. Dose proportionality was assessed using oral doses ranging from 0.4 to 4.0 mg/kg, and multiple dosing was evaluated with daily oral doses of 0.8 mg/kg. Serial blood samples were collected, and plasma concentrations of ilunocitinib were measured using a validated LC–MS/MS method. Pharmacokinetic samples were also collected in field trials. Intravenous administration resulted in low plasma clearance (0.437 L/h/kg), a volume of distribution of 1.58 L/kg, and a terminal half‐life of 4.4 h. Oral administration led to rapid absorption ( T max usually ranging between 1 and 4 h) and higher bioavailability in fed dogs (80%) compared to fasted dogs (61%). The prandial effect observed in laboratory studies with single doses was not clinically relevant under field conditions. Exposure increased less than proportionally with increasing doses. No clinically relevant accumulation was observed with 0.8 mg/kg daily dosing. No sex‐based differences were observed. Altogether, ilunocitinib pharmacokinetics support a once‐daily oral dosing in dogs. Minimal accumulation, also confirmed in long‐term studies, further supports the safety of ilunocitinib with a daily dosing regimen.