1. Academic Validation
  2. Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

  • Vet Anaesth Analg. 2020 Jan;47(1):47-52. doi: 10.1016/j.vaa.2019.07.004.
Juhana M Honkavaara 1 Marja R Raekallio 2 Pernilla M Syrja 3 Bruno H Pypendop 4 Heather K Knych 5 Ira J Kallio-Kujala 2 Outi M Vainio 2
Affiliations

Affiliations

  • 1 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. Electronic address: jussi.honkavaara@helsinki.fi.
  • 2 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
  • 3 Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
  • 4 Department of Radiological and Surgical Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
  • 5 Kenneth L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Abstract

Objective: To quantify the peripheral selectivity of vatinoxan (L-659,066, MK-467) in dogs by comparing the concentrations of vatinoxan, dexmedetomidine and levomedetomidine in plasma and central nervous system (CNS) tissue after intravenous (IV) coadministration of vatinoxan and medetomidine.

Study design: Experimental, observational study.

Animals: A group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 ± 0.1 years (mean ± standard deviation).

Methods: All dogs were administered a combination of medetomidine (40 μg kg-1) and vatinoxan (800 μg kg-1) as IV bolus. After 20 minutes, the dogs were euthanized with an IV overdose of pentobarbital (140 mg kg-1) and both venous plasma and CNS tissues (brain, cervical and lumbar spinal cord) were harvested. Concentrations of dexmedetomidine, levomedetomidine and vatinoxan in all samples were quantified by liquid chromatography-tandem mass spectrometry and data were analyzed with nonparametric tests with post hoc corrections where appropriate.

Results: All dogs became deeply sedated after the treatment. The CNS-to-plasma ratio of vatinoxan concentration was approximately 1:50, whereas the concentrations of dexmedetomidine and levomedetomidine in the CNS were three- to seven-fold of those in plasma.

Conclusions and clinical relevance: With the doses studied, these results confirm the peripheral selectivity of vatinoxan in dogs, when coadministered IV with medetomidine. Thus, it is likely that vatinoxan preferentially antagonizes α2-adrenoceptors outside the CNS.

Keywords

MK-467; central nervous system; distribution; dog; medetomidine; vatinoxan.

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