Objective

To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.

Study design

Prospective single-group interventional study.

Animals

A group of six healthy adult research ponies (four mares, two geldings).

Methods

Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg^–1) and butorphanol (0.01 mg kg^–1) for an unrelated study. Additional IV detomidine (0.004 mg kg^–1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg^–1) and ketamine (2.2 mg kg^–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg^–1) with fenpipramide (0.0125 mg kg^–1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05).

Results

Plasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg^–1 and plasma clearance 7.77 ± 1.98 mL minute^–1 kg^–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration.

Conclusions and clinical relevance

Administration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.

中文翻译：

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l-美沙酮在异氟醚麻醉和机械通风小马中的药代动力学和药效学

客观的

评估市售的l-美沙酮/芬哌酰胺组合对异氟醚麻醉小马的药代动力学和选定的药效学作用。

学习规划

前瞻性单组干预研究。

动物

一组六匹健康的成年研究小马（四匹母马，两只骟马）。

方法

在一项无关的研究中，小马用静脉 (IV) 地托咪定 (0.02 mg kg ^–1 ) 和布托啡诺 (0.01 mg kg ^–1 )镇静。85 分钟后给予额外的 IV 地托咪定 (0.004 mg kg ^–1 )，然后使用 IV 地西泮 (0.05 mg kg ^–1 ) 和氯胺酮 (2.2 mg kg ^–1 )诱导麻醉。用氧气中的异氟醚维持麻醉。在稳定的异氟醚麻醉 15 分钟后获取基线读数。l -美沙酮（0.25 mg kg ^–1）与芬哌胺（0.0125 mg kg ^–1) 然后进行静脉注射。每 10 分钟记录一次选定的心肺变量，并使用 Wilcoxon 符号秩检验与基线进行比较。记录不良事件。对于血浆浓度和药代动力学的分析动脉血浆样品升-methadone物在预定的时间点在整个麻醉收集。数据显示为平均值 ± 标准偏差或中位数和四分位距 ( p < 0.05)。

结果

l-美沙酮的血浆浓度显示出快速的初始分布阶段，然后是较慢的消除阶段，这在两室模型中得到了最好的描述。终末半衰期为 44.3 ± 18.0 分钟，分布容积为 0.43 ± 0.12 L kg ^–1，血浆清除率为7.77 ± 1.98 mL min ^–1 kg ^–1。平均动脉血压从基线时的 85 (±16) 增加到 100 (±26) 10 分钟后l-美沙酮/芬哌酰胺给药 ( p  = 0.031)。心率保持不变。两匹小马在施用l-美沙酮后的不同时间点发生束颤。

结论和临床相关性

一个行政升-methadone / fenpipramide组合异氟烷麻醉导致一过性血压升高，而不在心脏率增加并发小马。药动学升-methadone类似于那些报道给予外消旋美沙酮意识的马。