Infectious Diseases

Diclazuril quickly reaches therapeutic MIC levels in CSF

By Marie Rosenthal MS

A recent study found that diclazuril (Protazil, Merck Animal Health) reached the minimum inhibitory concentration (MIC) of Sarcocystis neurona in a horse’s cerebrospinal fluid (CSF) within 12 hours of 1 oral dose.

The MIC is the concentration of a drug in a bodily fluid necessary to kill or prevent growth of an organism. Diclazuril is a pelleted treatment used to treat equine protozoal myeloencephalitis (EPM), a neurological disease in horses caused primarily by S. neurona.

“Many older studies looking at diclazuril or other drugs for treatment of EPM frequently did not sample CSF, so they waited until the drugs had reached steady state in the plasma before getting to the CSF,” said Kate L. Hepworth-Warren, DVM, an assistant professor of equine internal medicine at North Carolina State University. “So, we knew that it eventually reach MICs of S. neurona in the CSF, but we did not know how quickly.”

EPM is a debilitating infection of the central nervous system (CNS), leading to signs such as asymmetrical ataxia, muscle atrophy, mentation changes and cranial nerve deficits. Up to 90% of the US horses have been exposed to S. neurona, although most exposed horses will not develop clinical disease. For those that progress to disease, up to 70% of horses show clinical improvement with early treatment.

The NC State University study involved 6 healthy adult horses that were neurologically normal and negative for EPM. Diclazuril levels in both plasma and CSF were measured frequently following a single oral dose of 1 mg/kg given with sweet feed, according to Dr. Hepworth-Warren. The goal was to determine how quickly diclazuril concentrations reached the MIC for S. neurona in the CSF of healthy horses.

They found that the diclazuril concentrations in the CSF surpassed the MIC for S. neurona (1 ng/mL) in all horses by 12 hours after consuming the dose.

The CSF concentrations peaked at 24 hours, whereas plasma concentrations took longer to increase. Not only did diclazuril reach the MIC quickly, but it remained above the MIC for 8 days, suggesting a sustained therapeutic effect may be possible, although more study is needed in this area, she said.

Rapid progression
Because affected horses can progress rapidly, Dr. Hepworth-Warren said that veterinarians often start treatment before a definitive diagnosis is made.

“Knowing that diclazuril reaches the MIC of S. neurona in the CSF very quickly, practitioners can feel comfortable that they can safely start initial treatment with diclazuril,” Dr. Hepworth-Warren said.

It is still important to do diagnostic testing to confirm the infection, however, she added. Where she practices, nearly 80% of horses are positive on serology, but not have clinical EPM, because the actual disease incidence is much lower. So, testing the CSF and serum is needed.

“It’s important to emphasize diagnostic testing,” Dr. Hepworth-Warren said. “Many horses are suspected of having EPM, and only a very small percentage actually do. Where I practice, for example, upward of 80% of horses will test positive on serum for antibodies toward S. nerona, but only an estimated 1% of horses actually have clinical EPM.”

However, she said, don’t wait to give that first dose. “A lot of times we start treating horses with suspected EPM before we have a definitive diagnosis because the disease can progress rapidly. So, we want to make sure that we can give them something that will be effective very quickly, because it can be rapidly progressive in some cases,” she said. MeV

FOR MORE INFORMATION
Treece EJ, Hepworth-Warren KL, Papich MG, et al. Pharmacokinetics of diclazuril in the plasma and cerebrospinal fluid of healthy adult horses after a single oral dose administered as a pelleted topdressing. J Vet Pharm Ther. 2026 May 16. https://doi.org/10.1111/jvp.70086.