Adam M, Raekallio M R, Keskitalo T, Honkavaara J M, Scheinin M, Kajula M, Mölsä S, Vainio O M
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Pharmacology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt.
J Vet Pharmacol Ther. 2018 Jun;41(3):447-456. doi: 10.1111/jvp.12486. Epub 2018 Jan 19.
The effect of MK-467, a peripheral α -adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2-week washout periods. Medetomidine (MED) 30 μg/kg alone or combined in the same syringe with MK-467 300 μg/kg (MMK) was injected intramuscular, followed by ATI 150 μg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. With MK-467, medetomidine plasma concentrations were threefold higher prior to ATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidine-related cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly when MK-467 was included. In this study, MK-467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement.
在八只绵羊中研究了外周α-肾上腺素能受体拮抗剂MK-467对肌肉注射美托咪定引起的血浆药物浓度、镇静作用及心肺变化的影响。此外，还评估了其与用于逆转的阿替美唑（ATI）之间的相互作用。采用随机前瞻性交叉设计，每只动物接受四次治疗，每次治疗间隔2周的洗脱期。单独肌肉注射30μg/kg美托咪定（MED）或在同一注射器中与300μg/kg MK-467联合（MMK），30分钟后肌肉注射150μg/kg阿替美唑（MED + ATI和MMK + ATI）或生理盐水。分析血浆中的药物浓度，并用视觉模拟量表主观评估镇静程度。在治疗前及之后的不同时间间隔测量全身血流动力学和血气。使用MK-467时，在注射阿替美唑之前美托咪定的血浆浓度高出三倍，这与更深的镇静作用和更短的起效时间相关。各治疗组之间早期心肺变化未观察到显著差异。两种治疗后阿替美唑均逆转了与美托咪定相关的心肺变化。当加入MK-467时，镇静评分下降更快。在本研究中，MK-467似乎对美托咪定的血浆浓度和中枢作用有显著影响，对心肺功能的改善较小。
