在马全血中选择的非甾体抗炎药物的体外和离体药效学。

In vitro and ex vivo pharmacodynamics of selected non-steroidal anti-inflammatory drugs in equine whole blood.

机构信息

Pharmacology and Toxicology Division, Department of Animal Pathology, Faculty of Veterinary Medicine, University of Turin, Italy.

出版信息

Vet J. 2012 Mar;191(3):327-33. doi: 10.1016/j.tvjl.2011.03.016. Epub 2011 May 11.

DOI:10.1016/j.tvjl.2011.03.016

PMID:21565533

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenases (COX), and the inhibition of COX-2 rather than COX-1 can limit the onset of NSAID-related adverse effects. The pharmacodynamic properties of eltenac, naproxen, tepoxalin, SC-560 and NS 398 in healthy horses were investigated using an in vitro whole blood assay. To predict COX selectivity in clinical use, eltenac and naproxen were also studied ex vivo after intravenous administration. SC-560 acted as a selective COX-1 inhibitor, tepoxalin as a dual inhibitor with potent activity against COX-1, and NS 398 as a preferential COX-2 inhibitor. Eltenac was a preferential COX-2 inhibitor in vitro but un-selective in the ex vivo study. Naproxen maintained its non-selectivity both in vitro and ex vivo. These findings have demonstrated that in vitro studies may not accurately predict in vivo NSAID selectivity for COX and should be confirmed using an ex vivo whole blood assay.

摘要

非甾体抗炎药（NSAIDs）抑制环氧化酶（COX），抑制 COX-2 而不是 COX-1 可以限制 NSAID 相关不良反应的发生。使用体外全血测定法研究了埃替拉芬、萘普生、替泊沙林、SC-560 和 NS 398 在健康马中的药效学特性。为了预测 COX 在临床使用中的选择性，还在静脉给药后进行了体外研究。SC-560 作为选择性 COX-1 抑制剂，替泊沙林作为对 COX-1 具有强效活性的双重抑制剂，而 NS 398 作为优先 COX-2 抑制剂。埃替拉芬在体外是优先 COX-2 抑制剂，但在体外研究中没有选择性。萘普生在体外和体内均保持非选择性。这些发现表明，体外研究可能无法准确预测 COX 的体内 NSAID 选择性，应使用体外全血测定法进行确认。