King Jonathan N, Panteri Alessandro, Graille Melanie, Seewald Wolfgang, Friton Gabriele, Desevaux Cyril
Companion Animal Development, Elanco Animal Health, Basel, Switzerland.
Preclinical, Elanco Centre de Recherche Santé Animale, St-Aubin, Switzerland.
BMC Vet Res. 2016 Jun 23;12(1):124. doi: 10.1186/s12917-016-0734-4.
Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days.
Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide.
The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.
血管紧张素转换酶抑制剂与非甾体抗炎药联合使用可能会在人类中诱发急性肾损伤，尤其是与利尿剂合用时。本研究的目的是评估贝那普利、罗贝考昔及其组合对健康猫的影响。在两项研究（研究1之后是研究2）中，每组32只健康猫被随机分为四组（每组4只雄性和4只雌性猫），采用平行组设计。各组每天口服一次，持续7天，分别给予安慰剂（对照组）、贝那普利、罗贝考昔或贝那普利加罗贝考昔。在研究2中，所有组还每天两次皮下注射0.5mg/kg速尿，持续7天。
贝那普利、罗贝考昔及其组合耐受性良好，这从缺乏临床症状以及对体重、采食量、临床化学、血液学和尿液分析指标无负面影响得到证明。该研究的主要终点是肾小球滤过率（GFR），通过碘海醇的血浆清除率来估计。在没有速尿的情况下，接受贝那普利加罗贝考昔组合的猫的GFR显著高于其他三组，仅接受贝那普利的雌性猫的GFR也显著高于对照组。速尿的给药诱导了利尿，降低了GFR并激活了肾素 - 醛固酮 - 血管紧张素系统，这从血浆肾素活性和血浆醛固酮浓度的增加可以看出。与接受速尿治疗的猫的对照组相比，贝那普利使GFR升高（仅雌性），而罗贝考昔使GFR降低（仅雄性）。贝那普利、罗贝考昔及其组合显著抑制了速尿诱导的血浆醛固酮的增加。
贝那普利和罗贝考昔的组合耐受性良好，在健康猫中无论有无速尿同时使用，对GFR要么升高要么有中性作用。贝那普利和罗贝考昔的组合降低了速尿引起的血浆醛固酮浓度升高。建议在患有临床疾病，尤其是蛋白尿性慢性肾病的猫中测试贝那普利和罗贝考昔联合使用的疗效和安全性。
