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

This research explores the effectiveness of a Cathepsin K inhibitor (VEL-0230) in reducing bone resorption in horses, and how the drug is processed in the body (pharmacokinetics). The results indicated a weekly dosage may effectively inhibit bone resorption and return to baseline levels one week after withdrawal, making it a viable treatment option.

Study Design

• The study involved monitoring the effects of different doses of VEL-0230 on plasma and urine drug and CTX-1 levels in adult horses.
• In the first stage, three horses received drugs at varying doses (2, 4, and 8 mg/kg body weight) in a Latin square design. This type of design is used in experiments to avoid the influence of two or more factors from distorting the results and was evaluated over a week.
• A dosage of 4 mg/kg body weight was selected for a dose interval study based on the pharmacokinetics of VEL-0230. This was evaluated over three administrations on the intervals of 3.25 days and 7 days with four exercising horses in the same design.

Results and Analysis

• The chosen dose intervals showed rapid inhibition of bone resorption, evident in plasma CTX-1 levels, a biomarker that indicates the rate of bone resorption.
• The level of CTX-1 inhibition before the next dose was administered was not different from baseline in both the 3.25 days and 7 days protocols, suggesting the treatment maintained its efficacy in repeated use.
• Beyond the first three days, the week-long protocol showed sustained CTX-1 inhibition. The cost effectiveness and logistical simplicity of weekly administration made the 7-day protocol preferable.

Conclusions

• The findings suggest that VEL-0230 could be a viable option for inhibiting bone resorption in horses when administered weekly. This could potentially have significant implications for disease management in horses prone to bone conditions.
• CTX-1 levels returned to baseline within a week after drug withdrawal, even after multiple doses, suggesting that the drug does not have lasting effects on the horse’s system once treatment is discontinued.