Ertapenem Pharmacokinetics in Equine Plasma and Synovial Fluid Following a Single Intravenous Dose.
Abstract: This study describes the pharmacokinetics of ertapenem, a carbapenem antimicrobial that has not been previously studied in equids. Administered as a 30 mg/kg intravenous bolus to six healthy horses, serial blood and synovial samples were obtained over 8 h after administration. Pharmacokinetic analysis of plasma and synovial fluid was performed. In plasma, the AUC was 353.10 h × μg/mL (CV = 49.02%), Vss 79.34 mL/kg (CV = 22.85%), CL 84.96 mL/h/kg (CV = 31.31%) and t1/2 2.03 h (CV = 15.32%). In synovial fluid, the AUC was 524.10 h × μg/mL (CV = 16.03%), VD 206.32 mL/kg (CV = 30.55%), CL 57.24 mL/h/kg (CV = 16.03%) and t1/2 2.50 h (CV = 32.47%). Synovial fluid maintained higher concentrations of ertapenem for longer, although exhibited a lower maximum concentration compared to plasma. The six most common surgical site infection isolates at a tertiary care center in equine orthopedic cases, and their susceptibility to ertapenem were evaluated. The isolates identified were largely consistent with previous reports. The drug was well tolerated, although it caused transient soft feces. Carbapenems remain a protected class of antimicrobials which should be reserved for cases where culture and susceptibility results support their administration. This study helps inform appropriate dosage and dosing intervals.
© 2026 John Wiley & Sons Ltd.
Publication Date: 2026-02-16 PubMed ID: 41697045DOI: 10.1111/jvp.70053Google Scholar: Lookup
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Summary
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Overview
- This study investigated how the antibiotic ertapenem behaves in the blood and joint fluid of healthy horses after a single intravenous dose.
- Its findings provide important information for determining safe and effective dosing of ertapenem in horses, especially for treating infections in joints.
Introduction to the Study
- Ertapenem is a carbapenem antibiotic, a class of drugs often reserved for serious infections due to their broad-spectrum activity and importance in human medicine.
- Prior to this research, the pharmacokinetics of ertapenem had not been studied in horses (equids).
- Understanding how the drug distributes and clears in horses is essential for safe and effective therapeutic use, especially for infections involving joints or surgical sites.
Methods
- Six healthy horses were given a single intravenous bolus of ertapenem at a dose of 30 mg/kg.
- Blood (plasma) and synovial fluid (joint fluid) samples were collected serially over an 8-hour period post-administration.
- Pharmacokinetic analysis was performed to assess drug concentration over time, volume of distribution, clearance rates, and half-life in both plasma and synovial fluid.
- Additionally, the study evaluated the susceptibility of common bacterial isolates from equine orthopedic surgical infections to ertapenem.
Key Pharmacokinetic Findings
- Plasma (blood) results:
- AUC (Area Under Curve): 353.10 h×μg/mL — represents overall drug exposure over time.
- Volume of distribution at steady state (Vss): 79.34 mL/kg — describing how the drug disperses in the body.
- Clearance (CL): 84.96 mL/h/kg — rate of drug elimination from plasma.
- Half-life (t1/2): Approximately 2.03 hours — the time for the drug concentration in plasma to reduce by half.
- Coefficient of Variation (CV) values indicate some variability among horses, especially for AUC and clearance.
- Synovial fluid (joint fluid) results:
- AUC: 524.10 h×μg/mL — higher total drug exposure in joint fluid compared to plasma.
- Volume of distribution (VD): 206.32 mL/kg — larger than plasma volume, indicating significant penetration into joint fluid.
- Clearance: 57.24 mL/h/kg — slower elimination from synovial fluid compared to plasma.
- Half-life: 2.50 hours — longer persistence in joint fluid than in plasma.
- The maximum drug concentration (Cmax) in synovial fluid was lower than in plasma, but concentrations remained higher for a longer period.
Clinical Implications
- The longer half-life and greater AUC in synovial fluid suggest ertapenem may maintain therapeutic concentrations in joints for an extended period after IV administration.
- This makes ertapenem potentially effective for treating joint infections or surgical site infections in horses.
- The six most common bacterial isolates from equine orthopedic surgical infections were tested, and susceptibility patterns were consistent with earlier reports, supporting the drug’s relevance in these infections.
- Ertapenem was generally well tolerated, although a transient side effect of soft feces was noted, which is important for monitoring during clinical use.
- The study emphasizes that carbapenems like ertapenem are a protected class of antibiotics and should be reserved for cases with confirmed bacterial susceptibility to avoid antimicrobial resistance development.
Conclusions and Recommendations
- This study fills a knowledge gap by providing pharmacokinetic data on ertapenem in horses, particularly regarding its behavior in plasma and synovial fluid.
- The findings guide veterinarians in making informed decisions about appropriate dosing and intervals of ertapenem to achieve effective and sustained drug levels, especially in joint infections.
- Given the importance of stewardship for carbapenem antibiotics, culture and susceptibility testing remain crucial before their clinical use.
- Further research might be needed to assess multiple dosing regimens, efficacy in actual infected horses, and safety over longer treatment courses.
Cite This Article
APA
Bish-Jones AR, Papich MG, Orsini JA.
(2026).
Ertapenem Pharmacokinetics in Equine Plasma and Synovial Fluid Following a Single Intravenous Dose.
J Vet Pharmacol Ther.
https://doi.org/10.1111/jvp.70053 Publication
Researcher Affiliations
- Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, USA.
- Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Grant Funding
- Roemer Foundation
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