Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3-4 days.
Authors: Hunyadi Laszlo, Papich Mark G, Pusterla Nicola
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary Diclazuril at a reduced dose of 0.5 mg/kg administered every 3–4 days may offer a practical alternative to standard dosing protocols for treating protozoal infections in horses, particularly equine protozoal myeloencephalitis caused by *Sarcocystis neurona* and *Neospora caninum*. Researchers administered five doses of 1.56% diclazuril pellets to six healthy adult horses, collecting plasma samples at trough (pre-dose) and peak (10 hours post-dose) timepoints, then analysed drug concentrations using high-pressure liquid chromatography and nonlinear mixed-effects modelling. Mean steady-state peak concentrations reached 0.284 µg/mL with a terminal half-life of 1.6 days, though considerable inter-individual variation was observed—critically, these levels exceeded the minimum inhibitory concentrations for both *S. neurona* (0.001 µg/mL) and *N. caninum* (0.1 µg/mL). For practitioners, these findings suggest that extended-interval, low-dose diclazuril regimens may sustain therapeutic plasma concentrations whilst potentially reducing cumulative drug exposure and associated costs, though individual pharmacokinetic variability warrants careful monitoring of clinical response and consideration of plasma concentration testing where available.
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Practical Takeaways
- •Low-dose diclazuril pellets given every 3-4 days can maintain therapeutic plasma concentrations against protozoal parasites, offering a practical dosing schedule for equine practitioners
- •Individual variation in half-life is substantial, so plasma monitoring may be warranted for horses not responding clinically to standard dosing
- •This regimen provides cost-effective prophylaxis and treatment for S. neurona and N. caninum in adult horses
Key Findings
- •Low-dose diclazuril (0.5 mg/kg) administered every 3-4 days achieved mean peak plasma concentration of 0.284 μg/mL in adult horses
- •Mean terminal half-life was 1.6 days with large inter-individual variation
- •Steady-state concentrations achieved were sufficient to inhibit both S. neurona (requiring 0.001 μg/mL) and N. caninum (requiring 0.1 μg/mL)
- •Trough concentrations remained above inhibitory thresholds for both parasites despite 3-4 day dosing intervals