Pharmacokinetics and bone resorption evaluation of a novel C athepsin K inhibitor ( VEL ‐0230) in healthy adult horses

Plasma pharmacokinetic ( PK ) and bone resorption biomarker [carboxy‐terminal cross‐linking telopeptide of type I collagen ( CTX ‐1)] analyses were performed following single and multiple oral dose protocols of a C athepsin K inhibitor ( VEL ‐0230) in horses. Outcomes included plasma and urine drug and CTX ‐1 concentrations. In the dose range study, 2, 4, and 8 mg/kg body weight (b.w.) doses were administered in a Latin square design to three mares and evaluated for 1 week. Based on the PK characteristics of VEL ‐0230, 4 mg/kg b.w. was selected for the dose interval study in which 3.25 days (d) and 7 days dose intervals were evaluated over three administrations using four exercising horses in a Latin square design. The 3.25 days and 7 days dose intervals provided a rapid inhibition of bone resorption based on plasma CTX ‐1. CTX ‐1 inhibition prior to next dose administration was not different from baseline in the 3.25 days and 7 days protocols, and for the first 3 days but the sustained CTX ‐1 inhibition in the 7 days protocol along with the cost and logistic benefits for weekly administration made the 7 days protocol preferable. Weekly administration of VEL ‐0230 may provide effective inhibition of bone resorption in young exercising horses that returns to baseline within 7 days after drug withdrawal even after multiple doses.