Pharmacokinetics of multiple doses of chloramphenicol in fed adult horses.
Authors: Estell K E, Knych H K, Patel T, Edman J M, Magdesian K G
Journal: Veterinary journal (London, England : 1997)
Summary
# Chloramphenicol Dosing in Horses: A Troubling Pharmacokinetic Gap Chloramphenicol is commonly prescribed orally to horses at 50 mg/kg every 6 hours, yet until this 2020 study, nobody had actually confirmed whether this dosing achieves therapeutic drug concentrations against susceptible pathogens. Estell and colleagues administered the standard oral dose to seven healthy adult horses for four days, collecting blood samples throughout to measure drug levels and determine whether steady-state concentrations would exceed the established antimicrobial breakpoint of 8.0 μg/mL. Results were disappointing: whilst peak concentrations varied widely between individuals (2.1–42.7 μg/mL), the average maximum was only 7.7 μg/mL, and the drug remained above the therapeutic threshold for just 75 minutes per six-hour dosing interval—far short of the 50% target needed for efficacy. Most concerning, the reliably achievable steady-state concentration across the population was merely 2.0 μg/mL, leaving many horses substantially underdosed against organisms that are technically susceptible at 8.0 μg/mL or higher. For equine practitioners, this finding raises serious questions about oral chloramphenicol's clinical utility at conventional doses and suggests the antimicrobial breakpoint itself may need recalibration for horses, or that dosing regimens require substantial revision to achieve adequate therapeutic coverage.
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Practical Takeaways
- •Chloramphenicol at the standard 50 mg/kg q6h dose may not achieve adequate therapeutic concentrations against organisms with the standard susceptibility breakpoint in horses; consider alternative antimicrobials or dosing strategies
- •High inter-individual variability in chloramphenicol concentrations between horses means some animals will achieve even lower plasma levels than the study average, further reducing clinical efficacy
- •When chloramphenicol is necessary, practitioners should be aware that therapeutic drug monitoring may be warranted, and susceptibility breakpoints used in equine practice may need to be lower than standard laboratory cutoffs
Key Findings
- •Maximum chloramphenicol concentration was highly variable between horses (2.1-42.7 μg/mL) when administered at 50 mg/kg PO q6h
- •The highest average steady-state concentration achieved was 7.7 μg/mL, just below the antimicrobial susceptibility breakpoint of 8.0 μg/mL
- •Average time above the 8.0 μg/mL breakpoint was only 75 minutes, considerably less than the recommended 50% of the dosing interval (180 minutes)
- •The established susceptibility breakpoint of 8.0 μg/mL is not reliably achievable in adult horses at the recommended dose, suggesting the breakpoint should be re-evaluated for equine medicine