Pharmacokinetics and Safety of a Single Subcutaneous or Intramuscular Dose of Ketamine in Healthy Horses.
Abstract: Pharmacokinetics (PK) of intramuscular (IM) and subcutaneous (SC) ketamine in horses has not been described. This study aimed to evaluate the PK and safety of ketamine and its metabolites after a single SC or IM administration. In Phase 1, two horses received 0.5 or 1 mg/kg of ketamine via SC and IM routes. In Phase 2, eight horses received 0.5 mg/kg IM. Plasma or serum concentrations of ketamine and major metabolites were determined by a validated liquid chromatography-mass spectrometry method at baseline and selected intervals post-administration. Subcutaneous administration resulted in extremely low concentrations (< 5 ng/mL). Phase 2 focused only on IM administration. Median peak serum ketamine concentrations after IM administration were 20.9 ng/mL (IQR 15.2-35.9) with a time to peak drug concentration of 1.4 h (IQR = 0.8-1.9 h) and terminal half-life of 1.8 h (IQR = 1.3-2.6 h). No changes in physical examination or laboratory parameters were observed. Ketamine metabolites were detected within 5 min after IM administration, with norketamine as the predominant metabolite. A single IM administration in healthy horses resulted in rapid absorption and variable inter-individual concentrations without adverse effects. Future studies should investigate repeated IM dosing and determine therapeutic plasma concentrations in horses.
© 2025 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
Publication Date: 2025-12-03 PubMed ID: 41340189PubMed Central: PMC12968486DOI: 10.1111/jvp.70037Google Scholar: Lookup
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- Journal Article
- Clinical Trial
- Veterinary
Summary
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Overview
- This study investigated how ketamine, a drug commonly used for anesthesia, is absorbed and processed in healthy horses after a single injection given either under the skin (subcutaneous, SC) or into the muscle (intramuscular, IM).
- It also examined the safety of these administration routes by monitoring drug levels in the blood and checking for any adverse effects.
Introduction and Purpose
- Ketamine is a widely used anesthetic in veterinary medicine, including in horses.
- The pharmacokinetics (PK)—how the drug is absorbed, distributed, metabolized, and eliminated—of intramuscular (IM) and subcutaneous (SC) ketamine in horses had not been well described before this study.
- This research aimed to describe the PK profile and safety of ketamine and its metabolites following a single SC or IM dose in healthy horses.
Study Design and Methods
- Conducted in two phases:
- Phase 1: Two horses were given ketamine at doses of 0.5 or 1 mg/kg via both SC and IM routes, to compare absorption and blood concentrations.
- Phase 2: Eight horses were given a single 0.5 mg/kg IM ketamine dose to further investigate PK parameters and safety.
- Blood samples (plasma or serum) were collected at baseline and various time points after dosing.
- A validated liquid chromatography-mass spectrometry (LC-MS) method was used to measure ketamine and its major metabolites, especially norketamine (a primary ketamine metabolite).
- Physical examinations and laboratory tests were performed to assess safety and detect any adverse effects.
Key Findings: Pharmacokinetics
- Subcutaneous (SC) administration:
- Ketamine concentrations were extremely low (<5 ng/mL), indicating poor absorption or rapid clearance from this route.
- Due to these low concentrations, Phase 2 focused only on the IM route.
- Intramuscular (IM) administration:
- Median peak serum ketamine concentration was 20.9 ng/mL, with an interquartile range (IQR) of 15.2-35.9 ng/mL, indicating variable absorption among individual horses.
- Time to reach peak concentration (Tmax) was a median of 1.4 hours (IQR 0.8-1.9 hours), showing relatively rapid absorption through the muscle.
- Terminal half-life (time for the drug concentration to reduce by half during elimination phase) was approximately 1.8 hours (IQR 1.3-2.6 hours), indicating moderate duration in the body.
- Metabolites, particularly norketamine, appeared quickly—within 5 minutes of IM injection—confirming rapid metabolism.
Safety Assessment
- No notable changes in physical examination findings or laboratory parameters were observed after ketamine administration.
- This suggests a favorable safety profile for a single IM dose of ketamine at 0.5 mg/kg in healthy horses.
- No adverse effects were reported during the monitoring period.
Conclusions and Future Directions
- Single IM injection of ketamine at 0.5 mg/kg achieves rapid absorption with variable peak concentrations among horses but no observable adverse effects.
- Subcutaneous administration at studied doses results in negligible ketamine systemic availability, making IM injection preferable for effective dosing.
- Future research should focus on:
- Repeated IM dosing regimens to understand accumulation or variability over time.
- Defining therapeutic plasma concentration ranges specific to horses, to optimize dosing for clinical efficacy and safety.
Cite This Article
APA
Rangel A, Sellon DC, Sanz MG, Pinnell E, Pietras ZM, Villarino NF.
(2025).
Pharmacokinetics and Safety of a Single Subcutaneous or Intramuscular Dose of Ketamine in Healthy Horses.
J Vet Pharmacol Ther, 49(2), 141-149.
https://doi.org/10.1111/jvp.70037 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
MeSH Terms
- Animals
- Horses / blood
- Horses / metabolism
- Ketamine / pharmacokinetics
- Ketamine / administration & dosage
- Ketamine / adverse effects
- Ketamine / blood
- Ketamine / analogs & derivatives
- Injections, Intramuscular / veterinary
- Injections, Subcutaneous / veterinary
- Male
- Female
- Half-Life
- Analgesics / pharmacokinetics
- Analgesics / administration & dosage
- Analgesics / adverse effects
- Analgesics / blood
- Area Under Curve
Grant Funding
- McEachern Endowment of Washington State University
Conflict of Interest Statement
The authors declare no conflicts of interest.
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