Spanish and Brazilian researchers recently assessed whether firocoxib—a non-steroidal anti-inflammatory drug (NSAID) that selectively blocks an enzyme called cyclooxygenase-2 (COX-2)—could effectively treat persistent mating-induced endometritis (PMIE, when the mare’s normal inflammatory response to clear her uterus post-breeding doesn’t go away as it should within 12 hours) in mares without serious side effects. Their results, said Marco Antonio Alvarenga, PhD, of the Department of Animal Reproduction and Veterinary Radiology at Sao Paulo State University, in Botucatu, Brazil, were promising.
Targeting the Right Enzyme
What’s tricky about using NSAIDs to manage PMIE is that they often target two kinds of cyclooxygenases, known as COX-1 and COX-2, said Alvarenga. COX-2 signals the endometrium (uterine lining) to create the prostaglandins that induce inflammation—this is the enzyme veterinarians aim to block when treating mares with PMIE. COX-1, on the other hand, calls for the production of prostaglandins involved with other processes, including the stomach lining’s protective mucus, blood flow in the kidneys, chemical balance in the circulatory system, and normal reproductive function—including ovulation. Ideally, he said, veterinarians want to use an NSAID that affects COX-2, but not COX-1, in broodmares.
Firocoxib does just that, said Alvarenga. “The advantage of firocoxib (compared to other NSAIDs) is that since it allows COX-1 activity to be preserved, it can be used long-term with no gastrointestinal side effects and no disturbance of the ovulation process,” he said.
Researchers at the Graf Lehndorff Institute in Neustadt, Germany, detected these side effects and disturbances while testing an NSAID called vedaprofen for treating PMIE back in 2010. While it’s considered selective for COX-2, it’s “not as selective” as firocoxib, Alvarenga explained. “Vedaprofen has a preferential activity for COX-2, but it can also inhibit COX-1,” he said.
In that study, vedaprofen ultimately led to anovulatory follicle production (follicles with no egg) in some mares, said Graf Lehndorff director Christine Aurich, PhD. “This (later) side effect was unknown when we performed the study,” she told The Horse.
“It’s true that firocoxib is very selective in inhibiting only COX-2,” she added. “In addition, it’s a very popular drug for horses because it’s well-tolerated with regard to gastrointestinal side effects.”
Alvarenga and his fellow researchers conducted two random experiments to assess firocoxib’s safety and efficacy in broodmares. First, they tested 20 healthy Quarter Horse mares over two consecutive estrous cycles, one without treatment and one with daily firocoxib treatment between ovulation and the day after insemination. (Resulting embryos were flushed.) As such, the mares served as their own controls.
In the second experiment, the scientists tested nine PMIE mares over two consecutive estrous cycles, with or without firocoxib treatment between ovulation and insemination. (They, too, served as their own controls.) They measured inflammation levels by testing intrauterine fluid and analyzing endometrial cytology and biopsies.
Alvarenga said firocoxib had no effect on ovulation or embryo production in healthy mares and that it reduced post-insemination inflammation in the PMIE mares.
Effective, Safe, but not a Fix-All
“Firocoxib is as good as other NSAIDs in controlling uterine inflammation, but with the advantage of being safe for the mares’ health and without disturbing the ovulation and fertilization processes,” Alvarenga said.
Even so, he cautioned practitioners against considering it an independent solution to PMIE. “Firocoxib must be used in combination with other support therapies such as PRP (platelet-rich plasma), uterine flush, and oxytocin for better control and resolution of uterine inflammation,” said Alvarenga.