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右美托咪定在异氟烷麻醉猫中静脉给药的药代动力学

Pharmacokinetics of dexmedetomidine administered intravenously in isoflurane-anesthetized cats.

作者信息

Escobar André, Pypendop Bruno H, Siao Kristine T, Stanley Scott D, Ilkiw Jan E

机构信息

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, 95616, USA.

出版信息

Am J Vet Res. 2012 Feb;73(2):285-9. doi: 10.2460/ajvr.73.2.285.

DOI:10.2460/ajvr.73.2.285
PMID:22280391
Abstract

OBJECTIVE

To determine the pharmacokinetics of dexmedetomidine administered as a short-duration IV infusion in isoflurane-anesthetized cats.

ANIMALS

6 healthy adult domestic female cats.

PROCEDURES

Dexmedetomidine hydrochloride was injected IV (10 μg/kg over 5 minutes [rate, 2 μg/kg/min]) in isoflurane-anesthetized cats. Blood samples were obtained immediately prior to and at 1, 2, 5, 6, 7, 10, 15, 30, 60, 90, 120, 240, and 480 minutes following the start of the IV infusion. Collected blood samples were transferred to tubes containing EDTA, immediately placed on ice, and then centrifuged at 3,901 × g for 10 minutes at 4°C. The plasma was harvested and stored at -20°C until analyzed. Plasma dexmedetomidine concentrations were determined by means of liquid chromatography-mass spectrometry. Dexmedetomidine plasma concentration-time data were fitted to compartmental models.

RESULTS

A 2-compartment model with input in and elimination from the central compartment best described the disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats. Weighted mean ± SEM apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state were 402 ± 47 mL/kg and 1,701 ± 200 mL/kg, respectively; clearance and terminal half-life (harmonic mean ± jackknife pseudo-SD) were 6.3 ± 2.8 mL/min/kg and 198 ± 75 minutes, respectively. The area under the plasma concentration curve and maximal plasma concentration were 1,061 ± 292 min•ng/mL and 17.6 ± 1.8 ng/mL, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

Disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats was characterized by a moderate clearance and a long terminal half-life.

摘要

目的

确定在异氟烷麻醉的猫中静脉短时间输注右美托咪定的药代动力学。

动物

6只健康成年家养雌性猫。

步骤

在异氟烷麻醉的猫中静脉注射盐酸右美托咪定(5分钟内注射10μg/kg [速率为2μg/kg/分钟])。在静脉输注开始前以及开始后1、2、5、6、7、10、15、30、60、90、120、240和480分钟采集血样。采集的血样转移至含有乙二胺四乙酸的试管中,立即置于冰上,然后在4℃下以3901×g离心10分钟。收集血浆并储存于-20℃直至分析。通过液相色谱-质谱法测定血浆右美托咪定浓度。右美托咪定血浆浓度-时间数据拟合至房室模型。

结果

具有中央房室输入和消除的二房室模型最能描述在异氟烷麻醉的猫中静脉短时间输注右美托咪定的处置情况。中央房室的加权平均±标准误表观分布容积和稳态时的表观分布容积分别为402±47 mL/kg和1701±200 mL/kg;清除率和终末半衰期(调和均值±刀切法伪标准差)分别为6.3±2.8 mL/分钟/kg和198±75分钟。血浆浓度曲线下面积和最大血浆浓度分别为1061±292分钟•纳克/毫升和17.6±1.8纳克/毫升。

结论及临床意义

在异氟烷麻醉的猫中静脉短时间输注右美托咪定的处置特点为清除率中等且终末半衰期长。

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