Journal of veterinary pharmacology and therapeutics2026; doi: 10.1111/jvp.70089

Characterization of the Pharmacokinetics and Physiological Effects of Tapentadol in Horses.

Lynch, AD
·
Mama, KR
·
McKemie, DS
·
Kass, PH
·
Knych, HK

Abstract: Tapentadol is a dual mechanism analgesic utilizing both μ-opioid receptor (MOR) agonism and norepinephrine reuptake inhibition (NRI). This study evaluated the pharmacokinetics and pharmacodynamics of tapentadol as a potential analgesic with the goal of treating pain in horses. Pharmacokinetics of both tapentadol and tapentadol-O-glucuronide were elucidated. Six horses received three separate escalating single oral doses (1, 3, and 5 mg/kg) and a single intravenous (0.32 mg/kg) dose of tapentadol in a four-period sequential design. Concentrations of tapentadol and tapentadol-O-glucuronide were determined using liquid chromatography-tandem mass spectrometry. The maximum concentrations (mean ± SD) in plasma following administration of 1, 3, 5 mg/kg oral tapentadol were 7.98 ± 6.95, 39.8 ± 53.8, and 210.6 ± 234.4 ng/mL at 0.75, 0.63, and 0.38 h, respectively. Maximum plasma concentration (mean ± SD) after a single 0.32 mg/kg IV dose was 339.2 ± 83.5 ng/mL. The maximum concentrations of tapentadol-O-glucuronide following single 1, 3, and 5 mg/kg oral doses and a single 0.32 mg/kg IV dose of tapentadol were 532.6 ± 171.4, 1169.4 ± 345.4, 1559.5 ± 574.6, and 226.4 ± 51.5 ng/mL at times 6.0, 6.0, 7.0, and 0.5 h. Tapentadol was well-tolerated at all doses.

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Publication Date: 2026-06-20 PubMed ID: 42322128DOI: 10.1111/jvp.70089Google Scholar: Lookup

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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.

Overview

This study investigated how tapentadol, a pain-relieving drug, is absorbed, metabolized, and tolerated in horses to assess its potential use for treating equine pain.
The research measured blood levels of tapentadol and its metabolite after different doses and looked at the drug’s safety profile in horses.

Background and Purpose

Tapentadol is an analgesic drug known for its dual mechanism of action: it acts as a μ-opioid receptor (MOR) agonist and also inhibits norepinephrine reuptake (NRI), making it effective for pain control in humans.
The study aimed to characterize the pharmacokinetics (how the drug is absorbed, distributed, metabolized, and excreted) and pharmacodynamics (the drug’s physiological effects) of tapentadol in horses.
Because horses have different metabolism and physiology compared to humans, it was important to understand how tapentadol behaves in this species before recommending it for equine pain management.

Study Design and Methods

Six healthy horses participated in the study.
A four-period sequential design was used, where each horse received all treatments separated by washout periods.
Treatments included three escalating single oral doses of tapentadol (1, 3, and 5 mg/kg) and a single intravenous (IV) dose of 0.32 mg/kg.
Blood samples were collected at multiple time points following each dose to measure concentrations of tapentadol and its primary metabolite, tapentadol-O-glucuronide.
Concentrations were determined using liquid chromatography-tandem mass spectrometry, a sensitive and specific analytical method.

Pharmacokinetic Findings

Oral tapentadol doses showed rapid absorption:
- Maximum plasma concentrations (Cmax) increased with higher doses:
  - 1 mg/kg: 7.98 ± 6.95 ng/mL at 0.75 hours
  - 3 mg/kg: 39.8 ± 53.8 ng/mL at 0.63 hours
  - 5 mg/kg: 210.6 ± 234.4 ng/mL at 0.38 hours
- The time to reach maximum concentration (Tmax) was relatively fast, indicating efficient oral absorption.
Following the IV dose, the maximum plasma concentration was higher (339.2 ± 83.5 ng/mL) due to direct administration into the bloodstream, and Tmax was faster (0.5 hours), as expected.
The metabolite tapentadol-O-glucuronide had later Tmax values, indicating it forms after tapentadol is metabolized:
- Oral doses had Tmax of 6.0-7.0 hours, with increasing Cmax corresponding to increasing doses:
  - 1 mg/kg: 532.6 ± 171.4 ng/mL
  - 3 mg/kg: 1169.4 ± 345.4 ng/mL
  - 5 mg/kg: 1559.5 ± 574.6 ng/mL
- IV dose maximum metabolite concentration occurred at 0.5 hours with a Cmax of 226.4 ± 51.5 ng/mL.

Physiological and Safety Observations

Tapentadol was well tolerated at all administered doses.
No adverse physiological effects were reported, suggesting tapentadol could be safe for use in horses at the studied doses.

Significance and Potential Applications

This research provides foundational knowledge on how tapentadol behaves in the equine body, important for dosing and safety guidelines.
The drug’s dual mechanism and good tolerability make it a promising candidate for managing pain in horses, which is a significant clinical need in veterinary medicine.
Further studies would be needed to evaluate the analgesic efficacy and optimal dosing regimens in painful equine conditions before clinical use.

Cite This Article

APA

Lynch AD, Mama KR, McKemie DS, Kass PH, Knych HK. (2026). Characterization of the Pharmacokinetics and Physiological Effects of Tapentadol in Horses. J Vet Pharmacol Ther. https://doi.org/10.1111/jvp.70089

Publication

Journal of veterinary pharmacology and therapeutics

ISSN: 1365-2885

NlmUniqueID: 7910920

Country: England

Language: English

Researcher Affiliations

Lynch, Annabella D

K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

Mama, Khursheed R

Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, USA.

McKemie, Dan S

K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

Kass, Phillip H

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Fort Collins, Colorado, USA.

Knych, Heather K

K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

Grant Funding

Center for Equine Health, School of Veterinary Medicine, University of California, Davis
Kenneth L Maddy Equine Analytial Chemistry Laboratory Program
T32GM144303 / NIH Pharmacology Training Grant

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