Background: Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may\ninduce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to\nevaluate the effects of benazepril, robenacoxib and their combination in healthy cats.\nIn each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n =4 male\nand 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo\n(control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition\n0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days.\nResults: Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs\nand no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables.\nThe primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma\nclearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of\nbenazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving\nonly benazepril compared to the control.\nAdministration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system,\nevidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group\nin cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males\nonly). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by\nfurosemide.\nConclusions: The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral\neffect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib\nreduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of\nthe combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.
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