King J N, Hotz R, Reagan E L, Roth D R, Seewald W, Lees P
Novartis Animal Health Inc., Clinical Development, Basel, Switzerland. Royal Veterinary College, Hawkshead Campus, Hatfield, Hertfordshire, UK.
J Vet Pharmacol Ther. 2012 Jun;35(3):290-300. doi: 10.1111/j.1365-2885.2011.01320.x. Epub 2011 Jul 8.
The safety of robenacoxib, a nonsteroidal anti-inflammatory drug with high selectivity for inhibition of the cyclooxygenase (COX)-2 isoform of COX, was investigated in the cat in two randomized, blinded, placebo-controlled, parallel-group studies. Robenacoxib was administered orally to healthy young domestic short-hair cats at dosages of 0 (placebo), 5 and 10 mg/kg once daily for 28 days (study 1) and at 0 (placebo), 2, 6 and 10 mg/kg twice daily for 42 days (study 2). The recommended minimum dosage for robenacoxib tablets in cats is 1 mg/kg once daily (range 1-2.4 mg/kg). Relative to placebo treatment, no toxicologically significant effects of robenacoxib were recorded in either study, based on general observations of health, haematological and clinical chemistry variables and urinalyses in life, and by post mortem organ weight, gross pathology and histopathology assessments. Pharmacokinetic-pharmacodynamic simulations indicated that all dosages of robenacoxib were associated with marked inhibition of COX-2 at peak effect (median I(max) 97.8-99.4% inhibition) with lesser inhibition of COX-1 (median I(max) 26.8-58.3% inhibition). Inhibition of the COXs was short lasting, with >10% median inhibition persisting for 4.0 h for COX-2 and 1.5 h for COX-1. These levels of inhibition of COX-1 and COX-2 twice daily with robenacoxib were not associated with any detectable toxicity, suggesting that, as previously described in dogs, the high safety index of robenacoxib in cats may be related to a combination of its high COX-2 selectivity and short residence time in the central compartment.
罗贝考昔是一种对环氧化酶（COX）-2同工型具有高选择性抑制作用的非甾体抗炎药，在两项随机、双盲、安慰剂对照、平行组研究中对猫进行了安全性研究。将罗贝考昔以0（安慰剂）、5和10mg/kg的剂量口服给予健康的年轻家养短毛猫，每日一次，持续28天（研究1），并以0（安慰剂）、2、6和10mg/kg的剂量每日两次，持续42天（研究2）。罗贝考昔片在猫中的推荐最小剂量为每日一次1mg/kg（范围为1-2.4mg/kg）。相对于安慰剂治疗，基于对健康、血液学和临床化学变量的一般观察以及生活中的尿液分析，以及死后器官重量、大体病理学和组织病理学评估，在两项研究中均未记录到罗贝考昔的毒理学显著影响。药代动力学-药效学模拟表明，罗贝考昔的所有剂量在峰值效应时均与COX-2的显著抑制相关（中位I(max)抑制率为97.8-99.4%），而对COX-1的抑制作用较小（中位I(max)抑制率为26.8-58.3%）。COX的抑制作用持续时间较短，COX-2的中位抑制率>10%持续4.0小时，COX-1持续1.5小时。罗贝考昔每日两次对COX-1和COX-2的这些抑制水平与任何可检测到的毒性均无关，这表明，如先前在犬中所描述的，罗贝考昔在猫中的高安全指数可能与其高COX-2选择性和在中央室的短停留时间的组合有关。
