Kaukinen H, Aspegrén J, Hyyppä S, Tamm L, Salonen J S
Orion Corporation, Orion Pharma, Turku, Finland Agrifood Research Finland, Ypäjä, Finland.
J Vet Pharmacol Ther. 2011 Feb;34(1):76-81. doi: 10.1111/j.1365-2885.2010.01193.x.
The objective of the study was to determine the absorption, bioavailability and sedative effect of detomidine administered to horses as an oromucosal gel compared to intravenous and intramuscular administration of detomidine injectable solution. The study was open and randomized, with three sequences crossover design. Nine healthy horses were given 40 μg/kg detomidine intravenously, intramuscularly or administered under the tongue with a 7-day wash-out period between treatments. Blood samples were collected before and after drug administration for the measurement of detomidine concentrations in serum. The effects of the route of administration on heart rate and rhythm were evaluated and the depth of sedation assessed. Mean (±SD) bioavailability of detomidine was 22% (±5.3%) after sublingual administration and 38.2% (±7.9%) after intramuscular administration. The sedative effects correlated with detomidine concentrations regardless of the route of administration. We conclude that less detomidine is absorbed when given sublingually than when given intramuscularly, because part of it does not reach the circulation. Sublingual administration of detomidine oromucosal gel at 40 μg/kg produces safe sedation in horses. Slow absorption leads to fewer and less pronounced adverse effects than the more rapid absorption after intramuscular injection.
本研究的目的是确定与静脉注射和肌肉注射地托咪定注射液相比，将地托咪定制成口腔黏膜凝胶给马使用时的吸收情况、生物利用度和镇静效果。该研究为开放性随机三序列交叉设计。9匹健康马分别接受40μg/kg地托咪定静脉注射、肌肉注射或舌下给药，每次治疗之间有7天的洗脱期。给药前后采集血样以测定血清中的地托咪定浓度。评估给药途径对心率和心律的影响，并评估镇静深度。地托咪定舌下给药后的平均（±标准差）生物利用度为22%（±5.3%），肌肉注射后为38.2%（±7.9%）。无论给药途径如何，镇静效果都与地托咪定浓度相关。我们得出结论，舌下给药时地托咪定的吸收量比肌肉注射时少，因为部分药物未进入循环。以40μg/kg的剂量给马舌下注射地托咪定口腔黏膜凝胶可产生安全的镇静效果。与肌肉注射后更快的吸收相比，缓慢吸收导致的不良反应更少且不那么明显。
