锦鲤（鲤属）浸泡于丙泊酚后的药代动力学和药效学效应

Pharmacokinetics and pharmacodynamic effects in koi carp (Cyprinus carpio) following immersion in propofol.

作者信息

Oda Ayako, Messenger Kristen M, Carbajal Liliana, Posner Lysa P, Gardner Brett R, Hammer Scott H, Cerreta Anthony J, Lewbart Gregory A, Bailey Kate M

机构信息

Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

出版信息

Vet Anaesth Analg. 2018 Jul;45(4):529-538. doi: 10.1016/j.vaa.2018.02.005. Epub 2018 Mar 12.

DOI:10.1016/j.vaa.2018.02.005

PMID:29705687

Abstract

OBJECTIVE

To test the hypothesis that plasma propofol concentration (PPC) is associated with anesthetic effect in koi carp administered propofol by immersion.

STUDY DESIGN

Prospective study.

ANIMALS

Twenty mature koi carp (mean ± standard deviation, 409.4 ± 83.7 g).

METHODS

Fish were immersed in propofol (5 mg L). Physiological variables and induction and recovery times were recorded. In phase I, blood was sampled for PPC immediately following induction and at recovery. In phase II, following induction, fish were maintained with propofol (4 mg L) via a recirculating system for 20 minutes. Following established induction, blood was sampled at 1, 10 and 20 minutes. In phase III (n = 19), fish were anesthetized as in phase II with blood sampled nine times in a sparse sampling strategy. Simultaneously, a pharmacodynamics rubric was used to evaluate anesthetic depth. PPC was determined using high performance liquid chromatography with fluorescence detection. Following evaluation of normality, data were analyzed using paired t test or Spearman correlation test (significance was set at p < 0.05).

RESULTS

In phase I, mean PPCs at induction (20.12 μg mL) and recovery (11.62 μg mL) were different (p < 0.001). In phase II, only mean PPCs at induction (17.92 μg mL) and 10 minutes (21.50 μg mL) were different (p = 0.013). In phase III, a correlation between PPCs and the pharmacodynamic rubric scores was found (p < 0.001, r = -0.93). There was no correlation between PPCs and recovery time (p = 0.057, r = 0.433). A two-compartment open model was chosen for the pharmacokinetic model. Absorption rate constant, elimination rate constant and intercompartmental rate constant were 0.48, 0.006 and 0.02 minute, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

Measurable PPCs were achieved in koi carp anesthetized with propofol by immersion. Anesthetic depth of fish was negatively correlated with PPCs, but recovery time was not.

摘要

目的

验证以下假设，即通过浸泡给予锦鲤丙泊酚时，血浆丙泊酚浓度（PPC）与麻醉效果相关。

研究设计

前瞻性研究。

动物

20条成熟锦鲤（平均±标准差，409.4±83.7克）。

方法

将鱼浸泡在丙泊酚（5毫克/升）中。记录生理变量以及诱导和恢复时间。在第一阶段，诱导后立即及恢复时采集血液样本用于测定PPC。在第二阶段，诱导后，通过循环系统用丙泊酚（4毫克/升）维持鱼体20分钟。诱导成功后，在1、10和20分钟采集血液样本。在第三阶段（n = 19），鱼体按照第二阶段的方法麻醉，采用稀疏采样策略采集9次血液样本。同时，使用药效学评分标准评估麻醉深度。采用高效液相色谱荧光检测法测定PPC。评估数据正态性后，使用配对t检验或Spearman相关检验进行数据分析（显著性设定为p < 0.05）。

结果

在第一阶段，诱导时的平均PPC（20.12微克/毫升）和恢复时的平均PPC（11.62微克/毫升）存在差异（p < 0.001）。在第二阶段，仅诱导时的平均PPC（17.92微克/毫升）和10分钟时的平均PPC（21.50微克/毫升）存在差异（p = 0.013）。在第三阶段，发现PPC与药效学评分标准得分之间存在相关性（p < 0.001，r = -0.93）。PPC与恢复时间之间无相关性（p = 0.057，r = 0.433）。药代动力学模型选择二室开放模型。吸收速率常数、消除速率常数和室间速率常数分别为0.48、0.006和0.02分钟。