First evidence of the incorporation of daprodustat and other hypoxia-inducible factor stabilizers into equine hair by passive transfer based on segmental quantitative analysis.

Introduction:

• Daprodustat is a medicine that inhibits hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD). Its role is to stimulate the production of red blood cells, which is helpful in treating anemia in humans.
• If horses are given daprodustat, they are banned for life from participating in equestrian sports and horseracing by two major international organizations.

Objective:

• The researchers wanted to investigate how long daprodustat and its byproducts can be detected in horse hair. This is important to monitor and prevent its misuse in horse sports. They compared this with how long the drug can be detected in plasma and urine.

Method:

• Three thoroughbred mares were given daprodustat through the nose and throat (nasoesophageal administration) for three days.
• Hair samples were taken from these horses over a 6-month period after giving them the drug. These samples were analyzed to detect the presence of daprodustat.

Results:

• A month after giving the drug, daprodustat was found mainly in the hair closest to the skin. Over the next six months, this drug trace moved along the hair shaft, matching the growth rate of horse mane hair.
• To understand how daprodustat gets into hair, 11 different parameters were studied, including how the drug behaves in the body (pharmacokinetics) and its physical and chemical properties. The major factors that influenced the drug’s presence in the hair were its maximum levels in the blood and its ability to dissolve in fats (lipophilicity). This suggests that daprodustat and similar drugs move from the bloodstream into the base of the hair through a natural process driven by concentration differences.
• This study provides the first evidence that HIF stabilizers, like daprodustat, get into hair in this way.
• Additionally, they compared how daprodustat is incorporated into horse hair with how another drug, roxadustat, is incorporated into human hair to gain insights into species differences.

Conclusion:

• The findings help in doping control, ensuring fair play in horse sports by monitoring the misuse of drugs like daprodustat. It also gives insights into how drugs get incorporated into horse hair, which can be useful for both anti-doping efforts and broader veterinary science.