Grimsrud K N, Mama K R, Thomasy S M, Stanley S D
K.L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Equine Vet J. 2009 Apr;41(4):361-5. doi: 10.2746/042516409x370900.
Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described.
To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses.
Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH-detomidine and COOH-detomidine were measured at predetermined time points using liquid chromatography-mass spectrometry.
Following i.v. administration, detomidine was distributed rapidly and eliminated with a half-life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10-18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215-687 ml/kg bwt, respectively. OH-detomidine was detected sooner than COOH-detomidine; however, COOH-detomidine had a much greater area under the curve.
These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.
右美托咪定常用于马匹静脉注射镇静和镇痛，但该药物的药代动力学和代谢情况尚未得到充分描述。
描述右美托咪定及其代谢产物3-羟基右美托咪定（OH-右美托咪定）和右美托咪定3-羧酸（COOH-右美托咪定）在马匹单次静脉注射和肌肉注射后的药代动力学。
八匹马用于平衡交叉设计研究。在第1阶段，4匹马接受30μg/kg体重的单次静脉注射右美托咪定，4匹马接受30μg/kg体重的单次肌肉注射。在第2阶段，处理方式互换。使用液相色谱-质谱法在预定时间点测量血浆中的右美托咪定、OH-右美托咪定和COOH-右美托咪定。
静脉注射后，右美托咪定迅速分布并消除，半衰期（t1/2(el)）约为30分钟。肌肉注射后，右美托咪定分布并消除，t1/2(el)约为1小时。静脉注射后，右美托咪定清除率的均值、中位数和范围分别为12.41、11.66和10.10 - 18.37 ml/min/kg体重。右美托咪定静脉注射的分布容积均值、中位数和范围分别为470、478和215 - 687 ml/kg体重。OH-右美托咪定比COOH-右美托咪定更早被检测到；然而，COOH-右美托咪定的曲线下面积大得多。
这些药代动力学参数为确定成熟马匹血浆中右美托咪定的峰值浓度和清除率提供了必要信息。结果表明，当需要更长的血浆浓度持续时间时，应考虑肌肉注射途径。
