title: Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL-0230) in healthy adult horses.
abstract: 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.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hussein
authors.forename: A
authors.initials: A
authors.lastname: Ishihara
authors.forename: M
authors.initials: M
authors.lastname: Menendez
authors.forename: A
authors.initials: A
authors.lastname: Bertone
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000662:veterinary*; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses / Q000378:metabolism / Q000502:physiology
chemical_list: D004852:Epoxy Compounds; C000599727:VEL-0230; D056657:Cathepsin K