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How Quickly Does Pelleted Diclazuril Reach Therapeutic Levels in Cerebrospinal Fluid, and Why is That Important for the Treatment of EPM?

By Kate Hepworth-Warren, DVM, DACVIM (LAIM)

Great question. With a progressive neurological disease like equine protozoal myeloencephalitis (EPM), the faster you begin treatment the better the outcome, especially in acute cases. Final test results can take a few days, or up to a week, so it is crucial to begin empirical treatment before they are available. Diclazuril is a first-line antiprotozoal agent against Sarcocystis neurona, but until now we haven’t had definitive data to understand when its concentration in cerebrospinal fluid (CSF) reaches the minimum inhibitory concentration (MIC) for this parasite. In other words, how quickly does it begin working?

A recent pharmacokinetic study conducted by our team at North Carolina State University fills that gap and offers practical guidance for equine practitioners.

The study involved six healthy adult horses that were neurologically normal and negative for EPM. We measured diclazuril levels in both plasma and CSF following a single oral dose administered at the labeled dose of 1 mg/kg top-dressed on sweet feed. Blood and CSF were collected at baseline then 1, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 and 192 hours post-administration.

KEY STUDY FINDINGS
A standout finding of this research is the speed at which diclazuril reached therapeutic levels in the CSF:

• MIC achievement: Diclazuril concentrations in the CSF surpassed the MIC of S. neurona (1 ng/mL) in all horses by 12 hours post-administration.
• Peak concentrations: The CSF concentrations peaked at 24 hours, while plasma concentrations peaked later at 48 hours. A horse with active EPM carries the parasite in the nervous system, which is why CSF concentrations are more valuable than blood levels alone.
• Prolonged therapeutic effect: Not only did diclazuril reach the MIC quickly, but it also remained well above the MIC through 8 days, suggesting a sustained therapeutic effect.

HOW DO I APPLY THIS TO EPM CASES IN MY PRACTICE?
The proven ability of diclazuril to reach therapeutic levels within 12 hours of one oral dose allows for prompt treatment of horses suspected to have clinical EPM. This can be especially critical in acute cases where time is of the essence. The study provides practitioners with added confidence in prescribing diclazuril as a first-line option for treating EPM.

When delivering an EPM diagnosis, it’s common for owners to feel anxious and impatient. Communicate that although clinical improvement may lag behind drug exposure, diclazuril rapidly establishes therapeutic levels in the horse. Emphasizing this swift onset can encourage owner compliance and patience during the initial treatment period. It remains important to follow the full treatment regimen, as indicated, for optimal therapeutic effect in horses with clinical EPM.

BOTTOM LINE
In acute cases, initiating diclazuril therapy early can give your patient the best possible head start against rapidly progressing disease. This concrete pharmacokinetic data can help you confidently guide EPM treatment protocols.

This research was presented at the 2025 International Veterinary Emergency & Critical Care Society Meeting.

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