Pharmacokinetic-Pharmacodynamic Study of Ampicillin-Cloxacillin Combination in Indian Thoroughbred Horses (Equus caballus) and Safety Evaluation of the Computed Dosage Regimen.
Authors: Kondampati Kasturi Devi, Saini Simrat Pal Singh, Sidhu Pritam K, Anand Arun, Kumar Deepesh, Beesam Srinu, Bedi Jasbir Singh, Kaur Rajdeep, Bhardwaj Rajesh
Journal: Journal of equine veterinary science
Summary
Appropriate antimicrobial dosing in equine practice requires pharmacokinetic-pharmacodynamic (PK-PD) integration tailored to individual populations, yet Indian Thoroughbreds lacked published guidance for the ampicillin-cloxacillin combination commonly used clinically. Using high-performance liquid chromatography and non-compartmental analysis, researchers administered a single 10 mg/kg IV dose to six horses and characterised elimination kinetics (ampicillin AUC 15.2 µg·h/ml, cloxacillin AUC 18.0 µg·h/ml) alongside minimum inhibitory concentrations against *Escherichia coli* and *Staphylococcus aureus* (0.4 µg/ml for both). PK-PD modelling indicated that the clinically relevant target (%T>MIC of ≥50%) necessitates a higher dosage than typically administered: 15 mg/kg (7.5 mg/kg each agent) every 12 hours rather than standard protocols. The recommended regimen proved haematologically and biochemically safe across 16 parameters monitored, supporting its clinical implementation in horses with susceptible bacterial infections. For practitioners, these findings suggest current dosing strategies may be subtherapeutic in Indian Thoroughbreds, with implications for treatment efficacy and antimicrobial stewardship in equine populations with similar pharmacokinetic profiles.
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Practical Takeaways
- •For treating bacterial infections in horses with ampicillin-cloxacillin combination, administer 15 mg·kg⁻¹ (7.5 mg·kg⁻¹ of each component) intravenously every 12 hours
- •This dosage regimen is safe with no adverse effects on standard biochemical and haematological parameters monitored in treated horses
- •Dosing should target bacteria with MIC ≤0.4 µg·ml⁻¹, covering common pathogens like E. coli and S. aureus
Key Findings
- •Ampicillin demonstrated AUC of 15.2 ± 0.54 µg·h·ml⁻¹ and cloxacillin AUC of 18.0 ± 0.9 µg·h·ml⁻¹ in Indian thoroughbred horses following 10 mg·kg⁻¹ IV dose
- •MIC of ampicillin-cloxacillin combination against E. coli and S. aureus was 0.4 µg·ml⁻¹
- •Recommended dosage regimen is 15 mg·kg⁻¹ (7.5 mg·kg⁻¹ each drug) IV every 12 hours to maintain %T>MIC of 50%
- •Recommended dosage regimen produced no significant alterations in 16 biochemical and haematological parameters