Kongara Kavitha, Chambers John Paul
Animal Welfare Science and Bioethics Centre, School of Veterinary Science, Massey University, Palmerston North, New Zealand,
Vet Med (Auckl). 2018 Aug 15;9:53-61. doi: 10.2147/VMRR.S170893. eCollection 2018.
Robenacoxib is a novel nonsteroidal anti-inflammatory drug (NSAID) of coxib class developed for the control of inflammation and pain in dogs and cats. It shows high selectivity for the cyclooxygenase-2 (COX-2) enzyme in rats, cats, and dogs. Robenacoxib is available in both injectable and tablet formulations. This review initially focuses on the preclinical pharmacology of robenacoxib in rats that includes its high affinity for COX-2 enzyme and weaker and rapidly reversible binding for COX-1 enzyme in in vitro and ex vivo models of inflammation and its pharmacokinetics in the blood and inflammatory exudate, selective tissue distribution, and safety. These basic pharmacological profiles highlight the suitability of robenacoxib for use in target species, such as cats and dogs. Since the level of expression and activity of COX enzymes is species specific, COX-2-selective inhibition and the resultant effects of coxibs must be studied in target species. The pharmacological and toxicological profiles of robenacoxib in cats and dogs have been discussed prior to reviewing its clinical efficacy and safety. Large, multicenter field trials conducted in cats and dogs demonstrated the noninferior efficacy and safety of robenacoxib compared with noncoxib NSAIDs used in dogs and cats. These trials investigated the efficacy of robenacoxib against various acute and chronic painful conditions. Robenacoxib produced superior efficacy to placebo and COX-2 preferential inhibitors in postsurgical cats. The tissue-selective anti-inflammatory activity of robenacoxib has been demonstrated in dogs with osteoarthritis. Robenacoxib has also been shown to be safe in healthy dogs and cats receiving antihypertensive drugs and loop diuretics that could cause renal injury. The developmental objective of coxibs, comparable efficacy but superior safety to less selective/nonselective NSAIDs, is well established with robenacoxib in preclinical studies. More studies need to be conducted to fully explore the benefits of robenacoxib in clinical subjects.
罗贝考昔是一种新型的环氧化酶-2(COX-2)抑制剂类非甾体抗炎药(NSAID),用于控制犬猫的炎症和疼痛。它在大鼠、猫和犬中对环氧化酶-2(COX-2)酶表现出高选择性。罗贝考昔有注射剂和片剂两种剂型。本综述首先聚焦于罗贝考昔在大鼠中的临床前药理学,包括其在体外和体内炎症模型中对COX-2酶的高亲和力以及对COX-1酶较弱且快速可逆的结合,其在血液和炎性渗出液中的药代动力学、选择性组织分布和安全性。这些基本药理学特征突出了罗贝考昔在犬猫等目标物种中的适用性。由于COX酶的表达水平和活性具有物种特异性,因此必须在目标物种中研究COX-2选择性抑制作用以及COX-2抑制剂的最终效果。在回顾罗贝考昔的临床疗效和安全性之前,先讨论了其在犬猫中的药理学和毒理学特征。在犬猫中进行的确大型多中心现场试验表明,与用于犬猫的非COX-2抑制剂类NSAID相比,罗贝考昔的疗效和安全性不逊色。这些试验研究了罗贝考昔对各种急慢性疼痛病症的疗效。在术后猫中,罗贝考昔的疗效优于安慰剂和COX-2选择性抑制剂。罗贝考昔在患骨关节炎的犬中已证明具有组织选择性抗炎活性。在接受可能导致肾损伤的抗高血压药物和袢利尿剂的健康犬猫中,罗贝考昔也已证明是安全的。在临床前研究中,罗贝考昔已充分确立了COX-2抑制剂类药物的研发目标,即疗效与非选择性/非特异性NSAID相当,但安全性更高。需要进行更多研究以充分探索罗贝考昔在临床受试者中的益处。