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猫口服透皮咪达唑仑凝胶后的药代动力学、镇静和血液动力学变化。

Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats.

机构信息

Quartet Veterinary Specialty and Emergency Hospital, Cary, NC, USA.

Texas A&M University, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, College Station, TX, USA.

出版信息

J Feline Med Surg. 2020 Dec;22(12):1184-1190. doi: 10.1177/1098612X20917305. Epub 2020 Jul 9.

Abstract

OBJECTIVES

The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables.

METHODS

Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate ( R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired -test or appropriate non-parametric tests.

RESULTS

Sedation occurred in all cats, and was increased from baseline at 30 mins ( <0.001). Decreases in HR occurred from 15-60 mins, ranging from 140 to 165 beats per min ( <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins ( = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins ( = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins).

CONCLUSIONS AND RELEVANCE

OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.

摘要

目的

本研究旨在描述健康猫口服经口腔黏膜(OTM)替马咪定凝胶的药代动力学,并评估其对镇静和血液动力学变量的影响。

方法

8 只体重为 4.12kg±0.72kg 的成年猫在颊黏膜上接受 4mg/m 替马咪定凝胶。给药后预定时间间隔评估镇静水平、心率(HR)、血压(BP)和呼吸频率(R)。通过内侧隐静脉导管采集血样以检测血浆替马咪定浓度和静脉血气变量。使用超高效液相色谱-质谱法分析血浆替马咪定浓度,并采用房室模型法获得药代动力学参数。使用方差分析和配对 t 检验或适当的非参数检验进行数据分析。

结果

所有猫均出现镇静,且在 30 分钟时(<0.001)从基线增加。HR 从 15-60 分钟下降,范围从 140 到 165 次/分钟(<0.001)。血糖从 101±12mg/dl 增加到 60 分钟时的 168±27.3mg/dl(=0.004)。收缩压从基线(139±14.8mmHg)下降到 60 分钟时的 103±23.0mmHg(=0.023)。所有变化在 120 分钟时消失。7/7 只猫在凝胶给药后 2 分钟内出现呕吐。清除率的几何平均值(变异系数)为 220.7ml/min/kg(35.3ml/min/kg),分布容积为 14.9l/kg(39.9l/kg)(均为生物利用度的函数),消除半衰期为 46.9min(16.0min)。替马咪定的最大血浆浓度为 10.5ng/ml(35.5ng/ml),在 36.9min(21.5min)时达到。

结论和相关性

OTM 替马咪定凝胶在健康猫中产生了中度镇静作用,副作用最小,尽管所有猫都出现了呕吐。药代动力学特征支持该物种的短期、微创镇静。需要进一步研究来评估其在虚弱猫或全身麻醉前的安全性和可行性。

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