Measurement of Cyclooxygenase Products in Plasma as Markers for Inhibition of Cyclooxygenase Isoforms by Oral Meloxicam in New Zealand White Rabbits (Oryctolagus cuniculus )

新西兰白兔(Oyctolagus cuniculus)血浆中环氧合酶产物的测量,作为口服美洛昔康抑制环氧合酶异构体的标记

阅读:2
作者:Jasmine Y Sarvi, Sara M Gardhouse, Michael D Kleinhenz, Samuel E Hocker, Mikaela M Weeder, Shawnee R Montgomery, Tess A Rooney

Abstract

Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E&sub2; (PGE&sub2; ) and thromboxane (TxB&sub2;) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB&sub2; and PGE&sub2; plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE&sub2; concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.

特别声明

1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。

2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。

3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。

4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。