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肌肉注射阿法沙龙在中部鬃狮蜥(鬃狮蜥)体内的药代动力学和药效学:注射部位的影响

Pharmacokinetics and pharmacodynamics of intramuscular alfaxalone in central bearded dragons (Pogona vitticeps): effect of injection site.

作者信息

Shippy Sarah, Allgood Hillary, Messenger Kristen, Hernandez Jorge A, Gatson Bonnie, Martin de Bustamante Michelle G, Alexander Amy B, Wellehan James Fx, Johnson Alanna

机构信息

Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.

出版信息

Vet Anaesth Analg. 2023 May;50(3):280-288. doi: 10.1016/j.vaa.2023.02.010. Epub 2023 Feb 24.

DOI:10.1016/j.vaa.2023.02.010
PMID:36973133
Abstract

OBJECTIVE

To evaluate the pharmacodynamic effects and pharmacokinetics of a single intramuscular (IM) injection of alfaxalone in central bearded dragons (Pogona vitticeps) when injected at a cranial versus a caudal site.

STUDY DESIGN

Prospective, masked, randomized crossover study.

ANIMALS

A total of 13 healthy bearded dragons weighing 0.48 ± 0.1 kg.

METHODS

Alfaxalone (10 mg kg) was administered IM to 13 bearded dragons in the triceps muscle (cranial treatment) or the quadriceps muscle (caudal treatment) separated by 4 weeks. Pharmacodynamic variables included movement score, muscle tone score and righting reflex. Blood was obtained from the caudal tail vein using a sparse sampling methodology. Plasma alfaxalone concentrations were determined using liquid chromatography-mass spectrometry, and pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Differences in variables between injection sites were analyzed using a nonparametric Wilcoxon signed-rank test for paired data with significance set at p ≤ 0.05.

RESULTS

Time to loss of righting reflex score was not different, median (interquartile range), between cranial and caudal treatments [8 (5-11) and 8 (4-12) minutes, respectively, p = 0.72]. Time to recovery of righting reflex was also not different between cranial and caudal treatments [80 (44-112) and 64 (56-104) minutes, respectively, p = 0.75]. Plasma alfaxalone concentrations were not significantly different between treatments. The population estimate (95% confidence intervals) for volume of distribution per fraction absorbed was 1.0 (0.79-1.20) L kg, clearance per fraction absorbed was 9.6 (7.6-11.6) mL minute kg, absorption rate constant was 2.3 (1.9-2.8) minute and elimination half-life was 71.9 (52.7-91.1) minutes.

CONCLUSIONS AND CLINICAL RELEVANCE

Regardless of the injection site, IM alfaxalone (10 mg kg) produced reliable chemical restraint in central bearded dragons, appropriate for nonpainful diagnostic procedures or anesthetic premedication.

摘要

目的

评估单次肌内注射阿法沙龙在中部鬃狮蜥(鬃狮蜥)的头部与尾部注射部位时的药效学作用和药代动力学。

研究设计

前瞻性、盲法、随机交叉研究。

动物

总共13只健康的鬃狮蜥,体重0.48±0.1千克。

方法

对13只鬃狮蜥分别在肱三头肌(头部注射组)或股四头肌(尾部注射组)进行10毫克/千克阿法沙龙的肌内注射,两组注射间隔4周。药效学变量包括运动评分、肌张力评分和翻正反射。采用稀疏采样法从尾静脉采血。使用液相色谱 - 质谱法测定血浆阿法沙龙浓度,并采用非线性混合效应模型进行药代动力学分析。使用配对数据的非参数Wilcoxon符号秩检验分析注射部位之间变量的差异,显著性设定为p≤0.05。

结果

头部和尾部注射组翻正反射消失评分的时间无差异,中位数(四分位间距)分别为[8(5 - 11)分钟和8(4 - 12)分钟,p = 0.72]。头部和尾部注射组翻正反射恢复时间也无差异,分别为[80(44 - 112)分钟和64(56 - 104)分钟,p = 0.75]。两组间血浆阿法沙龙浓度无显著差异。每吸收分数的分布容积的群体估计值(95%置信区间)为1.0(0.79 - 1.20)升/千克,每吸收分数的清除率为9.6(7.6 - 11.6)毫升/分钟/千克,吸收速率常数为2.3(1.9 - 2.8)分钟,消除半衰期为71.9(52.7 - 91.1)分钟。

结论及临床意义

无论注射部位如何,肌内注射阿法沙龙(10毫克/千克)在中部鬃狮蜥中均能产生可靠的化学性制动作用,适用于无痛诊断程序或麻醉前用药。

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