Journal of veterinary pharmacology and therapeutics2026; doi: 10.1111/jvp.70118

Pharmacokinetics of Detomidine and Vatinoxan in Horses.

Pypendop, BH
·
Raekallio, MR
·
Karikoski, NP
·
Hakonen, N
·
Tapio, HA
·
Gracio Calvo, LA
·
Rinne, VM
·
Honkavaara, JM

Abstract: The pharmacokinetics of detomidine, vatinoxan, and their combination have not been previously characterized in detail in horses. Detomidine (20 μg/kg), vatinoxan (200 μg/kg), or their combination was administered intravenously to six horses according to a Latin square design. Blood was sampled at various times up to 480 min following administration. Plasma concentrations of detomidine, OH-detomidine, COOH-detomidine, and vatinoxan were measured using liquid chromatography/tandem mass spectrometry. Compartmental models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A 5-compartment model provided the best fit for detomidine and its metabolites, whereas the disposition of vatinoxan was best described by a 3-compartment model. The volume of distribution at steady state was 762 mL/kg for detomidine and 1422 mL/kg for vatinoxan. Total metabolic clearance was 21.6 mL/min/kg for detomidine and 7.1 mL/min/kg for vatinoxan. Clearance of detomidine into OH-detomidine and of OH-detomidine into COOH-detomidine was predicted to be 40 and 7% of their respective clearance. Covariates accounting for the effect of vatinoxan on several parameters improved the model, suggesting that administration of vatinoxan affects the disposition of detomidine. Similarly, covariates suggested that administration of detomidine affects the disposition of vatinoxan.

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Publication Date: 2026-10-29 PubMed ID: 42956173DOI: 10.1111/jvp.70118Google Scholar: Lookup

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Summary

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Detomidine and vatinoxan, alone and in combination, were studied to understand how they are processed in the bodies of horses, revealing detailed pharmacokinetic profiles and interactions between the two drugs.

Study Objective and Design

The research aimed to characterize the pharmacokinetics of detomidine, vatinoxan, and their combination in horses, which had not been detailed before.
Six horses were used in a Latin square design to receive detomidine (20 μg/kg), vatinoxan (200 μg/kg), or both intravenously in separate periods.
Blood samples were collected at multiple time points for up to 480 minutes post-administration to measure plasma drug concentrations.

Analytical Methods

Plasma concentrations of detomidine, its metabolites OH-detomidine and COOH-detomidine, and vatinoxan were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).
This high-sensitivity technique allowed precise quantification of the drugs and metabolites over time.

Pharmacokinetic Modeling

Nonlinear mixed-effect modeling was applied to the concentration-time data to describe the drugs’ disposition using compartmental models.
A 5-compartment model best described detomidine and its metabolites, indicating complex processes such as distribution, metabolism, and elimination.
Vatinoxan’s pharmacokinetics were best captured by a simpler 3-compartment model, reflecting its distribution and clearance characteristics in horses.

Key Pharmacokinetic Parameters

Volume of distribution at steady state (Vss) reflects how extensively the drug distributes into body tissues:
- Detomidine: 762 mL/kg
- Vatinoxan: 1422 mL/kg, indicating a larger tissue distribution compared to detomidine
Total metabolic clearance, representing the volume of plasma cleared per minute per kg body weight:
- Detomidine: 21.6 mL/min/kg
- Vatinoxan: 7.1 mL/min/kg, suggesting slower clearance compared to detomidine
Detomidine metabolism involved conversion to OH-detomidine and then to COOH-detomidine:
- 40% of detomidine clearance leads to formation of OH-detomidine
- 7% of OH-detomidine clearance leads to COOH-detomidine formation

Drug Interaction Effects

Statistical covariates indicated that when vatinoxan is administered with detomidine, it affects several pharmacokinetic parameters of detomidine, suggesting altered disposition.
Conversely, detomidine administration altered the pharmacokinetic profile of vatinoxan, demonstrating a bidirectional interaction between the two drugs.
These findings imply a pharmacokinetic interaction that may influence the efficacy or safety profiles when the drugs are used together in horses.

Implications and Conclusions

This study provides the first comprehensive pharmacokinetic characterization of detomidine, vatinoxan, and their combined use in horses.
The complex pharmacokinetic profiles and interaction effects highlight the need to consider these dynamics when using the drugs concomitantly in clinical equine practice.
Understanding these parameters can help optimize dosing strategies to maximize therapeutic benefits and minimize adverse effects.

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APA

Pypendop BH, Raekallio MR, Karikoski NP, Hakonen N, Tapio HA, Gracio Calvo LA, Rinne VM, Honkavaara JM. (2026). Pharmacokinetics of Detomidine and Vatinoxan in Horses. J Vet Pharmacol Ther. https://doi.org/10.1111/jvp.70118

Publication

Journal of veterinary pharmacology and therapeutics

ISSN: 1365-2885

NlmUniqueID: 7910920

Country: England

Language: English

Researcher Affiliations

Pypendop, B H

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

Raekallio, M R

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Karikoski, N P

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Hakonen, N

Faculty of Veterinary Medicine, Veterinary Teaching Hospital, University of Helsinki, Helsinki, Finland.

Tapio, H A

Faculty of Veterinary Medicine, Veterinary Teaching Hospital, University of Helsinki, Helsinki, Finland.

Gracio Calvo, L A

Faculty of Veterinary Medicine, Veterinary Teaching Hospital, University of Helsinki, Helsinki, Finland.

Rinne, V M

Admescope (Symeres Finland OY), Oulu, Finland.

Honkavaara, J M

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Grant Funding

Finnish Foundation for Veterinary Research
Vetcare

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