Department of Veterinary Clinical Sciences, College of Veterinary Medicine and The College of Pharmacy, The Ohio State University, USA.
Equine Vet J. 2013 Nov;45(6):721-5. doi: 10.1111/evj.12049. Epub 2013 Mar 12.
Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown.
To determine the pharmacokinetics and sedative effects of midazolam in horses.
Blinded, randomised, crossover design.
Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectrometry method. Heart and respiratory rates and indices of sedation, ataxia, and sensitivity to stimuli were recorded before and at predetermined times after midazolam administration.
Pharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6 ml/min/kg (range 6.1-15.2 ml/min/kg) and 10.4 ml/min/kg (range 8.4-17.6 ml/min/kg), and median volume of distribution at steady state was 2094 ml/kg (range 2076-2413 ml/kg) and 2822 ml/kg (range 2270-7064 ml/kg) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Median distribution half-life was 24 min (range 6-42 min) and 39 min (range 33.6-72 min) and median terminal half-life was 216 min (range 120-248 min) and 408 min (range 192-924 min) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Cardiorespiratory parameters and sedation scores did not change. Midazolam caused agitation, postural sway, weakness, and one horse became recumbent after the 0.1 mg/kg bwt dose.
Midazolam produces ataxia and postural sway of short duration after i.v. administration to horses. Sedation was not evident after midazolam administration. Drug redistribution is likely the primary mechanism for the termination of effect.
Midazolam produces muscle relaxation but not sedation in adult horses.
咪达唑仑被用于控制马的癫痫发作并增强肌肉松弛，但它的药代动力学尚不清楚。
确定咪达唑仑在马体内的药代动力学和镇静作用。
双盲、随机、交叉设计。
在至少 7 天的间隔内，通过交叉设计，以 0.05 或 0.1mg/kg 体重的剂量静脉内给予 6 匹马咪达唑仑。在给药前和预定时间点采集血样，直至给药后 24 小时。通过液相色谱串联质谱法测定血清咪达唑仑浓度。在咪达唑仑给药前后和预定时间点记录心率、呼吸率以及镇静、共济失调和对刺激的敏感性指标。
对每组 5 匹马的样本进行了药代动力学分析。总清除率中位数分别为 10.6ml/min/kg（范围 6.1-15.2ml/min/kg）和 10.4ml/min/kg（范围 8.4-17.6ml/min/kg），稳态时的分布容积中位数分别为 2094ml/kg（范围 2076-2413ml/kg）和 2822ml/kg（范围 2270-7064ml/kg），分别在 0.05mg/kg 和 0.1mg/kg 体重剂量后。分布半衰期中位数分别为 24 分钟（范围 6-42 分钟）和 39 分钟（范围 33.6-72 分钟），终末半衰期中位数分别为 216 分钟（范围 120-248 分钟）和 408 分钟（范围 192-924 分钟），分别在 0.05mg/kg 和 0.1mg/kg 体重剂量后。心肺参数和镇静评分没有变化。在 0.1mg/kg 体重剂量后，咪达唑仑引起躁动、姿势摇摆、虚弱，一匹马变得卧倒。
咪达唑仑静脉给药后，马会出现短暂的共济失调和姿势摇摆。咪达唑仑给药后未出现镇静作用。药物再分布可能是作用终止的主要机制。
咪达唑仑在成年马中产生肌肉松弛作用，但不产生镇静作用。
