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Journal Article
Observational Study, Veterinary
Concentrations of medetomidine enantiomers and vatinoxan, an α 2 -adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs.
Veterinary Anaesthesia and Analgesia 2020 January
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.
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.
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