Objective

Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E₂ receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma.

Study design

Experimental study.

Animals

A total of six healthy, adult mixed-breed mares weighing 502 ± 66 (397–600) kg and aged 14.8 ± 5.3 (6–21) years.

Methods

Mares were administered one dose of 2 mg kg^–1 grapiprant via nasogastric tube. Blood and urine samples were collected prior to and up to 48 hours after drug administration. Drug concentrations were measured using high-performance liquid chromatography.

Results

Grapiprant plasma concentrations ranged from 71 to 149 ng mL^–1 with the mean peak concentration (106 ng mL^–1) occurring at 30 minutes. Concentrations were below the lower limit of quantification (50 ng mL^–1) in four of six horses at 1 hour and in all six horses by 2 hours after drug administration. Grapiprant urine concentrations ranged from 40 to 4077 ng mL^–1 and were still detectable at 48 hours after administration.

Conclusions and clinical relevance

Currently, there are no published studies looking at the pharmacodynamics of grapiprant in horses. The effective concentration needed to control pain in dogs ranges 114–164 ng mL^–1. Oral administration of grapiprant (2 mg kg^–1) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted.

中文翻译：

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测定马的 grapiprant 血浆和尿液浓度。

客观的

非甾体抗炎药是组织中环氧合酶 (COX) 的抑制剂，在不同物种中用作治疗剂。Grapiprant 是 piprant 类化合物的成员，可拮抗前列腺素受体。它是一种高度选择性的 EP4 前列腺素 E ₂受体抑制剂，从而限制了由更广泛的 COX 抑制引起的潜在副作用。本研究的目的是确定批准的犬剂量是否会在马中产生可测量的浓度，并验证尿液和血浆中 grapiprant 的色谱分析方法。

学习规划

实验研究。

动物

共有六匹健康的成年混种母马，体重 502 ± 66 (397–600) 公斤，年龄 14.8 ± 5.3 (6–21) 岁。

方法

通过鼻胃管向母马施用一剂 2 mg kg ^{-1 grapiprant。}在给药前和给药后最多 48 小时收集血样和尿样。使用高效液相色谱法测量药物浓度。

结果

Grapiprant 血浆浓度范围为 71 至 149 ng mL ^–1，平均峰值浓度 (106 ng mL ^–1 ) 出现在 30 分钟。给药后 1 小时，六匹马中有四匹马的浓度低于定量下限 (50 ng mL ^–1 )，给药后 2 小时所有六匹马的浓度均低于定量下限 (50 ng mL –1 )。Grapiprant 尿液浓度范围为 40 至 4077 ng mL ^–1，给药后 48 小时仍可检测到。

结论和临床相关性

目前，没有发表的研究关注马匹的药效学。控制狗疼痛所需的有效浓度范围为 114–164 ng mL ^–1。在马中口服 grapirant (2 mg kg ^–1 ) 没有达到这些浓度。该剂量耐受性良好；因此，可以进行更大剂量的研究。