Effect of benazepril and robenacoxib and their combination on glomerular filtration rate in dogs.
Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury, especially when combined with diuretics. The objective of this investigation was to evaluate the effect of benazepril, robenacoxib and their combination in healthy dogs. In each of two studies (studies 1 and 2), 32 beagle dogs were randomized into one of four groups in a parallel-group design. Groups received once-daily oral treatment for 7 days with placebo, benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all dogs received additionally 2 mg/kg furosemide orally twice daily. The primary endpoint was the glomerular filtration rate (GFR) estimated from the plasma clearance of iohexol. Secondary endpoints included standard clinical monitoring and, in study 2, plasma renin activity, urine volume, specific gravity and aldosterone concentration and water intake. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system. Benazepril and robenacoxib, administered alone or in combination, were tolerated well, did not decrease GFR with or without co-administration of furosemide and significantly reduced urinary aldosterone concentrations. No increased risk of acute kidney injury was identified with the combination of benazepril and robenacoxib in healthy dogs. Different effects might occur in dogs with heart or renal disease.
Preclinical, Elanco Centre de Recherche Santé Animale, St-Aubin, Switzerland.
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Panteri
Preclinical, Elanco Centre de Recherche Santé Animale, St-Aubin, Switzerland.
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Kukk
Safety, Elanco Animal Health, Basel, Switzerland.
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Desevaux
Companion Animal Development, Elanco Animal Health, Basel, Switzerland.
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Seewald
Companion Animal Development, Elanco Animal Health, Basel, Switzerland.
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King
D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D004159:Diphenylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D014563:Urodynamics / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001552:Benzazepines; D004232:Diuretics; D010648:Phenylacetates; D000450:Aldosterone; D005665:Furosemide; D004159:Diphenylamine; D012083:Renin; C044946:benazepril; C551524:robenacoxib