Huuskonen Vilhelmiina, Restitutti Flavia, Honkavaara Juhana M, Raekallio Marja R, Männikkö Sofia, Scheinin Mika, Vainio Outi M
Am J Vet Res. 2020 Apr;81(4):299-308. doi: 10.2460/ajvr.81.4.299.
To determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone.
8 healthy Beagles.
Dogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 μg/kg], medetomidine [20 μg/kg] and vatinoxan [400 μg/kg], and medetomidine [40 μg/kg] and vatinoxan [800 μg/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments.
Plasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were noninferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20.
Results suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.
确定同时给予瓦替诺昔（vatinoxan）是否会影响美托咪定在犬体内的镇痛效果，所给剂量能使右旋美托咪定的循环浓度与单独使用美托咪定产生的浓度相似。
8只健康比格犬。
在一项随机交叉设计试验中，犬接受3次静脉注射治疗，每次实验之间有2周的洗脱期（美托咪定[20μg/kg]、美托咪定[20μg/kg]和瓦替诺昔[400μg/kg]、美托咪定[40μg/kg]和瓦替诺昔[800μg/kg]；分别为M20、M20V400和M40V800）。评估镇静作用、内脏和躯体痛觉感受以及血浆药物浓度。比较各治疗组之间以及不同时间点的躯体和内脏痛觉感受测量值和镇静评分。分析M20V400和M40V800的镇静、内脏镇痛和躯体镇痛效果相对于M20效果的非劣效性，并评估各治疗组之间血浆药物浓度数据的等效性。
给予M20和M40V800后血浆右旋美托咪定浓度相当。各时间点内各治疗组的镇静评分、内脏痛觉感受测量值和躯体痛觉感受测量值无显著差异。M20V400和M40V800的总体镇静效果以及M40V800的内脏镇痛效果不劣于M20产生的效果。注射后10分钟时M20V400的躯体镇痛效果以及注射后10分钟和55分钟时M40V800的躯体镇痛效果不劣于M20产生的效果。
结果表明，当血浆右旋美托咪定浓度与单独使用美托咪定产生的浓度相等时，与瓦替诺昔合用不会显著减弱美托咪定的内脏镇痛效果。对于躯体镇痛，在某些时间点检测到各治疗组具有非劣效性。
