Goodman Laura A, Torres Bryan T, Reynolds Lisa R, Budsberg Steven C
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Am J Vet Res. 2010 Sep;71(9):1067-73. doi: 10.2460/ajvr.71.9.1067.
To evaluate the effects of firocoxib, meloxicam, and tepoxalin administration in healthy cats by measuring the ability of stimulated tissues to synthesize eicosanoids ex vivo.
8 healthy adult male cats.
In a blinded, randomized, crossover study design, cats were treated with firocoxib (1 mg/kg, PO, q 24 h), meloxicam (0.05 mg/kg, PO, q 24 h), tepoxalin (5.0 mg/kg, PO, q 12 h), or a placebo for 8 days. Blood samples and gastric and duodenal mucosal biopsy specimens were collected on days 0 (baseline; immediately before treatment), 3, and 8 of each treatment period. Thromboxane B2 (TXB2) concentrations were measured in serum, and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations were measured in plasma. Prostaglandin E1 (PGE1) synthesis, PGE2 synthesis, and LTB4 concentrations were measured in mucosal biopsy specimens. A 21-day minimum washout period was observed between treatments. Repeated-measures analyses were performed.
Firocoxib and meloxicam administration resulted in a lower plasma PGE2 concentration than at baseline on days 3 and 8 of administration, whereas tepoxalin administration did not. Tepoxalin administration resulted in a lower serum TXB2 concentration and pyloric and duodenal PGE1 synthesis on both days, compared with baseline and placebo administration. Neither firocoxib nor meloxicam administration altered pyloric or duodenal PGE1 synthesis on either day, compared with placebo administration. Tepoxalin administration also resulted in lower pyloric mucosal LTB4 concentrations on both days, compared with baseline values.
Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase.
通过测量体外刺激组织合成类花生酸的能力,评估给予非罗考昔、美洛昔康和替泊沙林对健康猫的影响。
8只健康成年雄性猫。
采用盲法、随机、交叉研究设计,猫分别接受非罗考昔(1毫克/千克,口服,每24小时一次)、美洛昔康(0.05毫克/千克,口服,每24小时一次)、替泊沙林(5.0毫克/千克,口服,每12小时一次)或安慰剂治疗8天。在每个治疗期的第0天(基线;治疗前即刻)、第3天和第8天采集血样以及胃和十二指肠黏膜活检标本。测定血清中血栓素B2(TXB2)浓度,测定血浆中前列腺素E2(PGE2)和白三烯B4(LTB4)浓度。测定黏膜活检标本中前列腺素E1(PGE1)合成、PGE2合成及LTB4浓度。各治疗之间观察到至少21天的洗脱期。进行重复测量分析。
给予非罗考昔和美洛昔康后,给药第3天和第8天血浆PGE2浓度低于基线水平,而给予替泊沙林后未出现这种情况。与基线和给予安慰剂相比,给予替泊沙林导致第2天血清TXB2浓度以及幽门和十二指肠PGE1合成降低。与给予安慰剂相比,给予非罗考昔和美洛昔康在任一天均未改变幽门或十二指肠PGE1合成。与基线值相比,给予替泊沙林还导致第2天幽门黏膜LTB4浓度降低。
给予非罗考昔和美洛昔康对环氧合酶-1活性无影响,而给予替泊沙林导致环氧合酶-1和5-脂氧合酶受到抑制。