Grimsrud Kristin N, Mama Khursheed R, Steffey Eugene P, Stanley Scott D
K.L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616,, USA.
Vet Anaesth Analg. 2012 Jan;39(1):38-48. doi: 10.1111/j.1467-2995.2011.00669.x. Epub 2011 Nov 22.
To describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.
Prospective experimental trial.
Eight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.
Medetomidine (10 μg kg(-1) ) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.
Pharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL(-1) ) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg(-1) minute(-1) and a volume of distribution of 1854 ± 565 mL kg(-1). The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL(-1) approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.
Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.
描述静脉注射一剂美托咪定后马匹的药效学和药代动力学。
前瞻性试验。
8匹11.7±4.6（均值±标准差）岁、体重557±54千克的健康成年马。
静脉注射美托咪定（10μg/kg）。在给药前至给药后48小时的固定时间点采集血液样本。在给药后0分钟至24小时的预定时间点获取行为、生理和生化数据。还使用痛觉计测量对有害刺激的阈值反应。通过液相色谱 - 质谱法测定美托咪定浓度，并用于使用非房室和房室分析计算药代动力学参数。
药代动力学分析估计，美托咪定在给药后6.4±2.7分钟达到峰值（8.86±3.87ng/mL），在给药后165±77分钟最后一次检测到。美托咪定的清除率为39.6±14.6mL/kg·分钟，分布容积为1854±565mL/kg。消除半衰期为29.1±12.5分钟。给药后约1小时血糖浓度最高达到176±46mg/dL。给药后观察到心率、呼吸频率、肠鸣音、红细胞压积和总蛋白浓度降低。给药后10分钟内马匹头部从107±12厘米降至20±10厘米，并逐渐恢复正常。给药后马匹活动能力下降。给药后10至45分钟机械阈值升高，马匹对声音反应减弱。
静脉给药后的行为和生理效应与血浆中美托咪定浓度的药代动力学特征呈正相关。美托咪定给药后血糖浓度逐渐短暂升高。该药物的镇痛作用持续时间似乎非常短。
