Scientific Division of Vetoquinol, 70200 Lure, France.
Scientific Division of Vetoquinol, 70200 Lure, France.
Vet J. 2021 Apr;270:105625. doi: 10.1016/j.tvjl.2021.105625. Epub 2021 Feb 1.
Cimicoxib is a selective COX-2 inhibitor (coxib) registered for the treatment of pain and inflammation in dogs. Pharmacokinetics of some coxibs have been described in dogs and cats. In cats, total body clearance values are lower and terminal half-lives of the coxibs are longer than those in dogs. The aim of this work was to evaluate if this is also the case for cimicoxib. For this purpose, blood pharmacokinetics and urinary excretion after IV administration were compared between these species. The in vitro metabolism of cimicoxib was also evaluated using canine and feline microsomes. In canine and feline microsomes, the formation rate of demethyl-cimicoxib, a phase 1 metabolite, was decreased in presence of quinidine, a specific human cytochrome P450 (CYP)2D6 inhibitor. IC values were 1.6 μM and 0.056 μM with canine and feline microsomes, respectively. As quinidine was about 30 times more potent in feline microsomes, the affinity of cimicoxib to the enzyme was considered to be about 30 times lower than that in canine microsomes. Total body clearance (Cl) of cimicoxib, was 0.50 L/h kg in dogs and 0.14 L/h kg in cats (P < 0.01) and terminal half-life, T, was 1.92 and 5.25 h, respectively (P < 0.01). Dose eliminated in urine was 12.2% in dogs and 3.12% in cats (P < 0.01). Conjugated demethyl-cimicoxib represented 93.7% of this amount in dogs and 67.5% in cats. Thus cimicoxib, like other veterinary coxibs, was eliminated more slowly in cats. Both CYP2D15 (the canine ortholog of CYP2D6) and UDP-glucuronyltransferase enzyme systems have reduced ability to produce metabolites of cimicoxib in cats.
昔布考昔是一种选择性 COX-2 抑制剂（昔布），已注册用于治疗犬的疼痛和炎症。一些昔布在犬和猫中的药代动力学特征已有描述。在猫中，总清除率值较低，昔布的终末半衰期比犬长。本工作旨在评估昔布考昔是否也如此。为此，比较了这两个物种静脉给药后的血药动力学和尿排泄。还使用犬和猫微粒体评估了昔布考昔的体外代谢。在犬和猫微粒体中，在存在奎尼丁（一种特异性人细胞色素 P450（CYP）2D6 抑制剂）的情况下，昔布考昔的相 1 代谢产物去甲基昔布考昔的形成率降低。用犬和猫微粒体的 IC 值分别为 1.6 μM 和 0.056 μM。由于奎尼丁在猫微粒体中的效力约为犬微粒体中的 30 倍，因此昔布考昔与该酶的亲和力被认为比犬微粒体中的亲和力低约 30 倍。昔布考昔的总清除率（Cl）在犬中为 0.50 L/h/kg，在猫中为 0.14 L/h/kg（P <0.01），终末半衰期 T 分别为 1.92 和 5.25 h（P <0.01）。在犬中，尿液中消除的剂量为 12.2%，在猫中为 3.12%（P <0.01）。共轭去甲基昔布考昔在犬中占此量的 93.7%，在猫中占 67.5%。因此，像其他兽医昔布一样，昔布考昔在猫中消除更缓慢。CYP2D15（CYP2D6 的犬同源物）和 UDP-葡萄糖醛酸转移酶系统都降低了产生昔布考昔代谢物的能力。
