Administration Study of Bedinvetmab, an Antinerve Growth Factor Monoclonal Antibody, in Horses for Doping Control Purposes.

Overview

• This study investigates the pharmacokinetics of bedinvetmab, an anti-nerve growth factor monoclonal antibody originally developed for dogs, when administered to horses.
• The goal was to understand how this drug is eliminated in horses and to provide important information for doping control in equine sports.

Background and Rationale

• Monoclonal antibodies targeting nerve growth factor (NGF) are emerging treatments for pain management in both humans and animals, including acute and chronic pain conditions.
• Bedinvetmab is an anti-NGF monoclonal antibody specifically designed for use in dogs to relieve pain.
• In competitive horse sports, these therapy-based drugs raise concerns because they could be misused to mask pain, potentially violating animal welfare and the integrity of competitions.
• Before this study, little was known about how these antibodies behave in horses, particularly regarding how long they remain in the bloodstream and thus detectable for doping control.

Objective

• The primary aim was to administer bedinvetmab to horses and measure its plasma concentration over time to characterize its elimination profile.
• Understanding this profile helps in detecting misuse and setting regulations in veterinary sports doping control.

Methodology

• Three geldings (male horses) were given a subcutaneous dose of bedinvetmab.
• The plasma concentration of bedinvetmab was measured using a sophisticated generic method:
• Affinity purification with Protein A magnetic beads to isolate the antibody from plasma samples.
• Tryptic digestion to break down the antibody into identifiable peptides.
• Identification and quantification of a specific proteotypic peptide using capillary flow high performance liquid chromatography combined with high resolution tandem mass spectrometry (HPLC-HRMS).

Key Findings

• There was significant variability among the three horses in how bedinvetmab was processed:
• Maximum plasma concentrations (Cmax) ranged between approximately 0.97 to 6.0 μg/mL.
• Peak concentrations were generally reached 1-2 days after administration.
• Duration of detectability also varied markedly:
• In two horses, the monoclonal antibody was still detectable at 34 days post-administration, with estimated concentrations around 1.7–1.9 μg/mL.
• In the third horse, detection was only possible up to 5 days post-dose, with a concentration of 0.13 μg/mL at that time.
• The reasons for this wide inter-individual variability were not clarified, suggesting complex pharmacokinetics possibly influenced by factors like metabolism, immune response, or distribution differences.

Implications

• This research shows that monoclonal antibodies developed for other species, such as dogs, can have prolonged effects in horses.
• Given the long detectability of bedinvetmab in horse plasma, there is a significant risk that such drugs could be misused to mask pain over extended periods in competitive equine events.
• The study underscores the necessity for effective doping control measures specifically targeting therapeutic monoclonal antibodies like bedinvetmab in horses.
• It provides foundational data to establish detection windows and assay development for anti-NGF mAbs in veterinary anti-doping protocols.

Conclusion

• Bedinvetmab can remain in horse plasma for several weeks after a single subcutaneous dose.
• The high variability between individual horses highlights the complexity of monitoring such drugs in doping contexts.
• These results advocate for the inclusion of monoclonal antibodies such as bedinvetmab in doping control programs to maintain welfare and integrity in equine sports.