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在自然发生慢性跛行的成年马中,对乙酰氨基酚(扑热息痛)的药代动力学、临床疗效和安全性。

Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.

机构信息

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.

Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.

出版信息

Equine Vet J. 2024 Jan;56(1):202-214. doi: 10.1111/evj.13959. Epub 2023 Jun 7.

Abstract

BACKGROUND

Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness.

OBJECTIVES

To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness.

STUDY DESIGN

Longitudinal.

METHODS

Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC-MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated by body-mounted inertial sensor (BMIS) and 10-point subjective lameness score on day 21 and compared to untreated baseline evaluation on day 35. Clinicopathological analysis (n = 12), hepatic biopsy (n = 6) and gastroscopy (n = 6) were evaluated on days -1 and 22.

RESULTS

Maximum plasma acetaminophen concentration (C ) was 20.83 ± 10.25 μg/mL at time (T ) 0.40 ± 0.22 h on day 7. The C on day 21 was 17.33 ± 6.91 μg/mL with a T of 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post-treatment; Significant percent improvement was detected in PD for horses with hindlimb lameness at 1, 2 and 8 h post-treatment. There were no significant differences in gastroscopy or hepatic biopsy scores between days -1 and 22.

MAIN LIMITATIONS

Small sample size, multi-limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation.

CONCLUSIONS

In horses with naturally occurring chronic lameness, acetaminophen at 30 mg/kg produced a transient improvement in subjective lameness and BMIS evaluation. Acetaminophen may not be effective as a monotherapy. Acetaminophen was safe following 21 days of 30 mg/kg PO every 12 h, with no evidence of clinically significant changes in clinicopathological analysis, hepatic biopsy or gastric ulceration scores.

摘要

背景

在患有肌肉骨骼疼痛的马匹中,临床使用对乙酰氨基酚;然而,在患有慢性跛行的马匹中尚未进行研究。

目的

确定在患有自然发生的慢性跛行的马匹中,慢性给予对乙酰氨基酚的药代动力学、安全性和疗效。

研究设计

纵向研究。

方法

12 匹患有慢性跛行的成年马每 12 小时接受 30mg/kg PO 的对乙酰氨基酚治疗,共 21 天。在第 7 天和第 21 天通过 LC-MS/MS 和非房室药代动力学分析分析对乙酰氨基酚的血浆浓度。在第 21 天通过身体安装惯性传感器(BMIS)和 10 分主观跛行评分评估跛行,并与第 35 天未治疗的基线评估进行比较。在第-1 天和第 22 天评估临床病理分析(n=12)、肝活检(n=6)和胃镜检查(n=6)。

结果

第 7 天,最大血浆对乙酰氨基酚浓度(C)在时间(T)0.40±0.22 小时时为 20.83±10.25μg/mL。第 21 天 C 为 17.33±6.91μg/mL,T 为 0.67±0.26 小时。治疗后 2 和 4 小时,主观跛行评分显著改善;治疗后 1、2 和 8 小时,后肢跛行的马匹 PD 显著改善百分比。在第-1 天和第 22 天之间,胃镜检查或肝活检评分没有显著差异。

主要局限性

样本量小,多肢跛行的严重程度和病因不同,缺乏中间跛行评估。

结论

在患有自然发生的慢性跛行的马匹中,30mg/kg 的对乙酰氨基酚可使主观跛行和 BMIS 评估短暂改善。对乙酰氨基酚可能不是一种有效的单一疗法。在 21 天内每天 30mg/kg PO 每 12 小时给予对乙酰氨基酚是安全的,临床病理分析、肝活检或胃溃疡评分均无临床显著变化的证据。

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