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在用酒石酸布托啡诺进行预处理后,对新生马驹静脉注射一剂阿法沙龙后,阿法沙龙的血浆药代动力学和药效学。

Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate.

作者信息

Goodwin Wendy, Keates Helen, Pasloske Kirby, Pearson Martin, Sauer Ben, Ranasinghe Millagahamada G

机构信息

School of Veterinary Science, University of Queensland, Gatton, Qld, Australia Jurox Pty Ltd, Rutherford, NSW, Australia.

出版信息

Vet Anaesth Analg. 2012 Sep;39(5):503-10. doi: 10.1111/j.1467-2995.2012.00734.x. Epub 2012 May 30.

Abstract

OBJECTIVE

To determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate.

STUDY DESIGN

Prospective experimental study.

ANIMALS

Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg.

METHODS

Foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis.

RESULTS

The harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl(p) ) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg(-1) and 0.6 ± 0.2 L kg(-1) , respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively.

CONCLUSIONS

The anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life.

CLINICAL RELEVANCE

Alfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended.

摘要

目的

在新生马驹经酒石酸布托啡诺预处理后单次静脉注射阿法沙龙,以确定该神经甾体麻醉药的药代动力学和药效学。

研究设计

前瞻性实验研究。

动物

5匹临床健康的澳大利亚纯血马驹,平均年龄±标准差为12±3天,体重67.3±12.4千克。

方法

马驹用布托啡诺(0.05毫克/千克静脉注射)进行预处理,10分钟后静脉注射3毫克/千克阿法沙龙诱导麻醉。在整个麻醉过程中评估心肺变量(心率、呼吸频率、直接动脉血压、动脉血气)和麻醉深度的临床体征。在关键时间点采集静脉血样,使用液相色谱-质谱联用仪(LC/MS)测定阿法沙龙血浆浓度,并通过非房室药代动力学分析进行分析。

结果

阿法沙龙的谐波平均血浆消除半衰期(t½)为22.8±5.2分钟。观察到的平均血浆清除率(Cl(p))和分布容积(Vd)分别为19.9±5.9毫升/分钟·千克和0.6±0.2升/千克。总体而言,麻醉诱导和苏醒的质量良好,所有马驹的大多数监测生理变量在临床上均可接受,尽管有些马驹在卧倒后短时间内出现低氧血症。从诱导到首次移动和从诱导到站立的平均麻醉持续时间分别为18.7±7分钟和37.2±4.7分钟。

结论

在所研究的5匹马驹中,所使用的麻醉方案提供了可预测且一致的麻醉平面,对心血管的抑制作用最小。与成年马一样,阿法沙龙在马驹体内的消除半衰期较短。

临床意义

阿法沙龙似乎是马驹合适的麻醉诱导剂,药代动力学表明,持续输注时它可能适合提供更长时间的麻醉。建议补充氧气。

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