Pharmacokinetics/pharmacodynamics analysis of trimethoprim and sulfamethoxazole for methicillin-resistant Staphylococcus aureus infection after intravenous and per os administration in Thoroughbred horses.
Abstract: A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the dosage regimens of trimethoprim/sulfamethoxazole for methicillin-resistant Staphylococcus aureus (MRSA) infections after intravenous (IV) and per os (PO) administration in horses. Methods: Trimethoprim/sulfamethoxazole plasma concentrations were measured in six horses after a single IV administration of 15 mg/kg (2.5 mg/kg trimethoprim and 12.5 mg/kg sulfamethoxazole) and PO administration of 30 mg/kg (5.0 mg/kg trimethoprim and 25.0 mg/kg sulfamethoxazole). The data were modeled using a nonlinear mixed-effects model. The probability of target attainment (PTA) of the PK/PD target defined as the ratio of the area under the free plasma concentration-time curve to the minimum inhibitory concentration (MIC) over 25 h was calculated for 5000 horses using Monte Carlo simulations. Conclusions: Trimethoprim/sulfamethoxazole dosage regimens of 15 mg/kg IV and 30 mg/kg PO at the approved interval of q12h did not attain therapeutic targets for MRSA infections in horses. More frequent administration (q8h) may be necessary to achieve these targets. In addition, this standard dosage achieved only 90 % PTA against the MIC of 0.125/2.38 mg/L and did not achieve against the MIC for the CLSI breakpoint for humans (2.0/38 mg/L).
Copyright © 2025 Elsevier Inc. All rights reserved.
Publication Date: 2025-07-07 PubMed ID: 40633628DOI: 10.1016/j.jevs.2025.105640Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article discusses a study that evaluated the efficiency of specific trimethoprim/sulfamethoxazole dosage regimens in treating methicillin-resistant Staphylococcus aureus (MRSA) infections in horses, using a pharmacokinetics/pharmacodynamics (PK/PD) analytic approach.
Research Methodology and Data Modelling
- The study involved monitoring the plasma concentrations of trimethoprim/sulfamethoxazole in six horses. These drug concentrations were measured following both the administration via injection (intravenous or IV) and oral administration (per os or PO).
- The dosage given was 15mg/kg for IV administration and 30mg/kg for PO administration. These values were derived from the combination of trimethoprim and sulfamethoxazole dosages.
- The recorded data were processed using a nonlinear mixed-effects model which is a statistical method for analysing repeated measurements in both drug concentrations and data variation.
Evaluation of Probability of Target Attainment (PTA)
- The Probability of Target Attainment (PTA) refers to the chances of achieving a predetermined PK/PD target. In this study, the PK/PD target is defined as the ratio of the area under the free plasma concentration-time curve to the minimum inhibitory concentration (MIC) over 25 hours.
- The PTA was calculated through Monte Carlo simulations, a statistical technique that allows for the modelling of complex systems. The simulations were run on an estimated 5000 horses to ascertain the likelihood of the drug concentration achieving the target PK/PD ratio.
Conclusion
- A crucial finding of the study was that the dosage regimens of 15mg/kg IV and 30mg/kg PO, given every 12 hours, were not sufficient to attain therapeutic targets for MRSA infections in horses.
- To achieve the PK/PD target, it was suggested that more frequent administration (every 8 hours) may be necessary.
- Moreover, it was observed that the standard dosage only managed to achieve a 90 % PTA against an MIC of 0.125/2.38 mg/L, and didn’t hit the MIC for the Clinical & Laboratory Standards Institute (CLSI) breakpoint for humans (2.0/38 mg/L).
Cite This Article
APA
Kuroda T, Minamijima Y, Niwa H, Mita H, Nomura M, Ohta M.
(2025).
Pharmacokinetics/pharmacodynamics analysis of trimethoprim and sulfamethoxazole for methicillin-resistant Staphylococcus aureus infection after intravenous and per os administration in Thoroughbred horses.
J Equine Vet Sci, 152, 105640.
https://doi.org/10.1016/j.jevs.2025.105640 Publication
Researcher Affiliations
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Japan. Electronic address: taisuke.kuroda@equinst.go.jp.
- Laboratory of Racing Chemistry, Tochigi 320-0851, Japan.
- Microbiology Division, Equine Research Institute, Japan Racing Association, Japan.
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Japan.
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Japan.
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Japan.
Conflict of Interest Statement
Declaration of competing interest The authors declare that there were no conflicts of interest.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
