Objectives

To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses.

Study design

Prospective, randomized, crossover study.

Animals

A group of six adult healthy horses weighing 585.2 ± 58.7 kg.

Methods

Each horse was administered IV hydromorphone (0.025 mg kg^–1; treatment H0.025), hydromorphone (0.05 mg kg^–1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures anova with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation.

Results

Hydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute^–1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg^–1, 106 ± 21 mL minute^–1 kg^–1 and 8.0 ± 1.5 ng hour mL^–1, respectively.

Conclusions and clinical relevance

Hydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.

中文翻译：

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盐酸氢吗啡酮在健康马匹中的药代动力学和药效学。

目标

确定对马静脉内施用氢吗啡酮的生理和行为影响以及药代动力学特征。

学习规划

前瞻性，随机，交叉研究。

动物

一组六头成年健康马，体重585.2±58.7公斤。

方法

每匹马随机服用静脉内氢吗啡酮（0.025 mg kg ^–1；治疗H0.025），氢吗啡酮（0.05 mg kg ^–1；治疗H0.05）或0.9％生理盐水，冲洗期为7天。对于每种治疗，在5小时内记录生理，血液，腹部borborygmi评分和行为数据，并在24小时内总计排便。使用重复测量方差分析对数据进行分析，其显着性为p <0.05。在处理H0.05中收集血样，用于定量血浆氢吗啡酮和氢吗啡酮-3-葡萄糖醛酸，并随后进行药代动力学参数计算。

结果

氢吗啡酮的给药导致心率（HR）和收缩期动脉压（SAP）的剂量依赖性增加。给药后5分钟，在H0.05治疗中，HR和SAP分别为59±17次/ min ^-1和230±27mmHg。没有观察到呼吸频率，动脉气体或温度的临床相关变化。两种氢吗啡酮治疗的borborygmi评分在2小时内均低于基线值。粪便排出量在各治疗之间没有差异，也没有观察到腹部不适的迹象。记录的行为在治疗之间没有差异。对于氢吗啡酮，稳态时的分布体积，总系统清除率和曲线下面积的平均值±标准偏差，直到最后一次测量的浓度为1.00±0.29 L kg ^–1，分别为106±21 mL分钟^–1 kg ^–1和8.0±1.5 ng hour mL ^–1。

结论与临床意义

对健康马静脉注射氢吗啡酮可增加HR和SAP，降低腹部borborygmi且不影响粪便排出量。