阴道内给予马匹地托咪定凝胶的镇静效果及药代动力学评估。

Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses.

作者信息

Seddighi Reza, Knych Heather K, Cox Sherry K, Sun Xiaocun, Moorhead Kaitlin A, Doherty Thomas J

机构信息

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.

K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.

出版信息

Vet Anaesth Analg. 2019 Nov;46(6):772-779. doi: 10.1016/j.vaa.2019.06.002. Epub 2019 Jun 17.

DOI:10.1016/j.vaa.2019.06.002

PMID:31474339

Abstract

OBJECTIVES

To determine the sedative effects and pharmacokinetic profile of detomidine when administered intravaginally as a gel formulation to horses.

STUDY DESIGN

Randomized, crossover, masked experimental design.

ANIMALS

A group of six healthy adult mares (494 ± 56 kg).

METHODS

Mares were studied on two occasions and were administered either detomidine hydrochloride (10 μg kg) intravenously (treatment IV) or detomidine gel (40 μg kg) intravaginally (treatment IVG), separated by 1 week. Sedation, ataxia, muzzle-floor distance and heart rate (HR) were evaluated every 15 minutes for 240 minutes. Venous blood samples were collected at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360 minutes postadministration and were analyzed for detomidine and metabolites using liquid chromatography-tandem mass spectrometry. Measured variables were compared over time and between treatments using mixed model analysis. Correlation between drug plasma concentrations and muzzle-floor distance, and sedation and ataxia scores was determined using the Spearman correlation coefficient. Data are presented as mean ± standard error of the mean and p value was set at <0.05.

RESULTS

Sedation was shorter with IV (119 ± 16 minutes) than with IVG (188 ± 22 minutes). Ataxia scores remained greater than baseline for 90 and 135 minutes for treatments IV and IVG, respectively. HR was lower than baseline for 45 and 30 minutes for IV and IVG, respectively, but did not differ between treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment IVG was 8.57 ng mL, 0.37 hour and 25%, respectively. There was a significant correlation (r = 0.68) between plasma detomidine concentrations and sedation score.

CONCLUSIONS AND CLINICAL RELEVANCE

Detomidine gel administered intravaginally resulted in clinically important sedation and is a viable method for detomidine gel delivery in mares.

摘要

目的

确定将地托咪定制成凝胶制剂经阴道给药于马匹时的镇静效果和药代动力学特征。

研究设计

随机、交叉、盲法实验设计。

动物

一组6匹健康成年母马（494±56千克）。

方法

母马分两次接受研究，分别静脉注射盐酸地托咪定（10μg/千克）（静脉注射治疗组）或经阴道给予地托咪定凝胶（40μg/千克）（经阴道凝胶注射治疗组），两次给药间隔1周。在240分钟内每隔15分钟评估一次镇静、共济失调、口鼻距地面距离和心率（HR）。给药后15、30、45、60、90、120、150、180、240、300和360分钟采集静脉血样，使用液相色谱-串联质谱法分析地托咪定及其代谢产物。使用混合模型分析对测量变量随时间以及不同治疗组之间进行比较。使用Spearman相关系数确定药物血浆浓度与口鼻距地面距离、镇静和共济失调评分之间的相关性。数据以平均值±平均标准误差表示，p值设定为<0.05。

结果

静脉注射组的镇静时间（119±16分钟）短于经阴道凝胶注射组（188±22分钟）。静脉注射治疗组和经阴道凝胶注射治疗组的共济失调评分分别在90和135分钟内高于基线水平。静脉注射组和经阴道凝胶注射组的心率分别在45和30分钟内低于基线水平，但两组之间无差异。经阴道凝胶注射治疗组的地托咪定平均最大血浆浓度、达峰时间和生物利用度分别为8.57ng/mL、0.37小时和25%。血浆地托咪定浓度与镇静评分之间存在显著相关性（r=0.68）。