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绵羊和山羊口服地昔布的比较处置动力学。

Comparative disposition kinetics of oral deracoxib in sheep and goats.

机构信息

Department of Veterinary Medicine, University of Sassari, Sassari, Italy.

Department of Veterinary Medicine, Lebanese University, Beirut, Lebanon.

出版信息

J Vet Pharmacol Ther. 2024 Sep;47(5):390-395. doi: 10.1111/jvp.13444. Epub 2024 Mar 28.

DOI:10.1111/jvp.13444
PMID:38545834
Abstract

This study investigates the pharmacokinetics (PK) of deracoxib (DX), a selective COX-2 inhibitor, in sheep and goats following a single oral dose. DX, approved for dogs, holds potential as an alternative NSAID in small ruminants, particularly in light of heightened concern regarding abomasal ulceration. The study employed an oral administration of DX at a dose of 150 mg/head (sheep and goats), and plasma concentrations were determined after validating a high-performance liquid chromatography method, coupled to a UV detector. The PK parameters, including maximum plasma concentration (C ), time to reach C (T ), elimination half-life (t ), and area under the curve (AUC), were evaluated through non-compartmental analysis. Results showed detectable DX in plasma up to 48 h, with no observed adverse effects. No significant differences in any PK parameters were noted between sheep and goats. Notably, t values were relatively long, at 16.66 h for sheep and 22.86 h for goats. Despite the fact that both species exhibited comparable drug exposure, high individual variability was noted within each species, suggesting to take into account individual variations in response to DX treatment, rather than species-specific considerations. Additional research involving pharmacodynamics and multiple-dose studies is warranted to comprehensively assess the profile of DX in these species.

摘要

本研究旨在调查单次口服选择性 COX-2 抑制剂 deracoxib(DX)在绵羊和山羊体内的药代动力学(PK)。DX 已获犬类批准,有望成为小反刍动物的替代 NSAID,特别是鉴于人们对网胃溃疡的关注度日益提高。研究采用 150mg/头(绵羊和山羊)的 DX 口服剂量,并在验证高效液相色谱法与紫外检测器联用的方法后,测定了血浆浓度。通过非房室分析评估了包括最大血浆浓度(C )、达峰时间(T )、消除半衰期(t )和曲线下面积(AUC)在内的 PK 参数。结果表明,DX 在血浆中可检测到长达 48 小时,未观察到不良反应。绵羊和山羊之间的任何 PK 参数均无显著差异。值得注意的是,t 值相对较长,绵羊为 16.66 小时,山羊为 22.86 小时。尽管两种物种的药物暴露情况相似,但每个物种内均存在较高的个体变异性,这表明在考虑对 DX 治疗的反应时,应考虑个体差异,而不仅仅是物种特异性。需要开展涉及药效动力学和多剂量研究的进一步研究,以全面评估 DX 在这些物种中的特征。

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