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Journal of veterinary pharmacology and therapeutics2026; doi: 10.1111/jvp.70070

Pharmacokinetics of Intramuscularly Administered Ketamine at Subanaesthetic Dosage in Horses.

Abstract: Subanaesthetic doses of ketamine (0.5 mg kg) provide analgesia in several species, but there is limited information on the pharmacokinetics and clinical effects of intramuscularly administered ketamine in horses. This study investigated the pharmacokinetics of ketamine and norketamine, and evaluated clinical effects, ataxia, and vital parameters, following intramuscular and intravenous administration of 0.5 mg kg ketamine in nine healthy horses, using a randomized two-period crossover design with a 1-week washout period. Plasma concentrations were analyzed using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS). Ketamine pharmacokinetic parameters were calculated using a one-compartment model and norketamine using a noncompartmental model. After intravenous administration (n = 9), ketamine showed a C of 525 ± 290 ng mL, an AUC of 85.9 ± 54.7 ng·h mL, and a t of 0.1 ± 0.01 h. Following intramuscular administration (n = 7), ketamine plasma concentrations were below the limit of quantification (< 5 ng mL) except at a few early timepoints, preventing reliable pharmacokinetic analysis. Norketamine showed a C of 39.7 ± 32.3 ng mL and a t of 0.3 ± 0.18 h after intramuscular administration. All horses developed transient, mild-to-severe ataxia after intravenous administration, resolving within 15 min. This was not observed after intramuscular administration. Intramuscular ketamine administration (0.5 mg kg) shows a low systemic bioavailability (< 5%) but is well tolerated and has minimal adverse effects.
© 2026 John Wiley & Sons Ltd.
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Publication Date: 2026-03-31 PubMed ID: 41914129DOI: 10.1111/jvp.70070Google Scholar: Lookup
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  • Journal Article

Summary

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Overview

  • This study examined how ketamine, given in a low dose via intramuscular injection, is absorbed, distributed, and metabolized in horses, comparing it to intravenous administration.
  • It also evaluated the safety and clinical effects, such as ataxia (loss of coordination) and vital signs, following these administration routes.

Background and Purpose

  • Ketamine is used at subanaesthetic doses (0.5 mg/kg) to provide pain relief (analgesia) in various species.
  • Limited data exist regarding how ketamine behaves pharmacokinetically and clinically when administered intramuscularly (IM) in horses.
  • This study aimed to provide detailed pharmacokinetic data on ketamine and its metabolite norketamine after IM and intravenous (IV) administration, and to observe clinical safety and effects.

Study Design

  • Nine healthy horses participated in a randomized two-period crossover design, meaning all horses received both IM and IV treatments separated by a one-week washout period.
  • Ketamine was administered at 0.5 mg/kg either via IM or IV routes.
  • Blood samples were collected at various time points post-administration for measurement of ketamine and norketamine plasma concentrations.
  • Plasma concentrations were analyzed using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS), a highly sensitive analytical technique.

Pharmacokinetic Analysis

  • For IV administration, pharmacokinetic parameters used a one-compartment model for ketamine and a noncompartmental model for norketamine.
  • Key pharmacokinetic findings after IV administration included:
    • Peak ketamine plasma concentration (Cmax): approximately 525 ± 290 ng/mL
    • Area Under the Curve (AUC), reflecting overall drug exposure: 85.9 ± 54.7 ng·h/mL
    • Elimination half-life (t½): approximately 0.1 ± 0.01 hours
  • Following IM administration:
    • Ketamine plasma concentrations were mostly below the limit of quantification (<5 ng/mL), except briefly at early timepoints, making detailed pharmacokinetic analysis unreliable.
    • Norketamine showed a peak concentration of 39.7 ± 32.3 ng/mL and a half-life of 0.3 ± 0.18 hours.
    • These results suggest very low systemic bioavailability (<5%) of ketamine when given IM at this dose.

Clinical Effects and Safety

  • All horses showed mild to severe but transient ataxia (loss of coordination) following intravenous ketamine, resolving within 15 minutes.
  • No ataxia was observed after intramuscular administration, indicating a safer clinical profile via the IM route at this dose.
  • Vital parameters remained stable and no significant adverse effects occurred with IM ketamine administration.
  • Low systemic bioavailability via IM dosing may explain the lack of observable ataxia or major clinical effects.

Conclusions and Implications

  • Intramuscular administration of ketamine at 0.5 mg/kg in horses leads to minimal systemic absorption and thus very low plasma drug levels.
  • This route and dose are well tolerated with minimal adverse clinical effects, particularly no ataxia observed.
  • The low bioavailability suggests that IM ketamine at this dose may have limited systemic analgesic effects, and dosing or formulation adjustments may be necessary for clinical efficacy.
  • The findings are important for veterinary anesthesia and pain management, emphasizing the need to consider administration routes when using subanaesthetic ketamine in horses.

Cite This Article

APA
Vandaele Z, Flyps J, Cuypers C, De Baere S, Devreese M, Schauvliege S. (2026). Pharmacokinetics of Intramuscularly Administered Ketamine at Subanaesthetic Dosage in Horses. J Vet Pharmacol Ther. https://doi.org/10.1111/jvp.70070

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English

Researcher Affiliations

Vandaele, Zoë
  • Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Flyps, Jana
  • Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Cuypers, Charlotte
  • Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
De Baere, Siegrid
  • Department of Pathobiology, Pharmacology and Zoological Medicine, Laboratory of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Devreese, Mathias
  • Department of Pathobiology, Pharmacology and Zoological Medicine, Laboratory of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Schauvliege, Stijn
  • Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

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