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Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL-0230) in healthy adult horses

Authors

  • H. Hussein,

    Corresponding author
    1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
    • Hayam Hussein, Comparative Orthopedic Research Laboratory, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus, Ohio 43210, USA. E-mail: Hussein.57@osu.edu

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  • A. Ishihara,

    1. School of Veterinary Medicine, Azabu University, Kanagawa, Japan
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  • M. Menendez,

    1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
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  • A. Bertone

    1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
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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.

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