Dimaio Knych Heather K, Stanley Scott D
K. L. Maddy Equine Analytical Chemistry Laboratory, Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Am J Vet Res. 2011 Oct;72(10):1378-85. doi: 10.2460/ajvr.72.10.1378.
To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition.
12 adult racehorses.
Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography-mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration.
Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration.
A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively, should be adopted for sublingual administration of detomidine gel.
根据标签说明，对舌下给予右美托咪定凝胶的药代动力学和药效学进行表征，以制定赛马比赛前适当的停药指南。
12匹成年赛马。
马匹接受0.04 mg/kg右美托咪定的单次舌下给药。在给药前及给药后长达72小时采集血样。在右美托咪定给药后5天收集尿样。通过液相色谱-质谱法分析血浆和尿样，并使用非房室分析对所得数据进行分析。在右美托咪定给药后还评估了下颌至地面距离、心率和心律、葡萄糖浓度、红细胞压积和血浆蛋白浓度。
右美托咪定的平均±标准差终末消除半衰期为1.5±1小时。到24小时时，血浆中代谢物浓度低于检测限（右美托咪定、羧基右美托咪定和羟基右美托咪定分别为0.02、0.1和0.5 ng/mL）。到3天时，尿中右美托咪定及其代谢物浓度低于检测限（右美托咪定为0.05 ng/mL，羧基右美托咪定和羟基右美托咪定为0.10 ng/mL）。所有马匹在右美托咪定给药后均有不同程度的镇静作用。起效时间≤40分钟，镇静持续时间约为2小时。相对于0时的值，下颌至地面距离和心率显著降低。右美托咪定给药后，既往存在的房室传导阻滞的发生率增加且加重。
舌下给予右美托咪定凝胶时，血浆和尿样检测的停药期应分别采用48小时和3天。
