Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL-0230) in healthy adult horses
Version of Record online: 15 APR 2014
© 2014 John Wiley & Sons Ltd
Journal of Veterinary Pharmacology and Therapeutics
Volume 37, Issue 6, pages 556–564, December 2014
How to Cite
Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL-0230) in healthy adult horses. J. vet. Pharmacol. Therap. 37, 556–564., , ,
- Issue online: 14 NOV 2014
- Version of Record online: 15 APR 2014
- Manuscript Accepted: 17 MAR 2014
- Manuscript Received: 3 DEC 2013
- FreeStride Therapeutics, Inc.
- Thoroughbred Charities of America
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 Cathepsin 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.