title: Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Companion Animal Development, Elanco Animal Health, Basel, Switzerland. jonathan.king@elanco.com.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: King
authors.affiliation: Preclinical, Elanco Centre de Recherche Santé Animale, St-Aubin, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Panteri
authors.affiliation: Preclinical, Elanco Centre de Recherche Santé Animale, St-Aubin, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Graille
authors.affiliation: Companion Animal Development, Elanco Animal Health, Basel, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seewald
authors.affiliation: Companion Animal Development, Elanco Animal Health, Basel, Switzerland.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Friton
authors.affiliation: Safety, Elanco Animal Health, Basel, Switzerland.
authors.forename: Cyril
authors.initials: C
authors.lastname: Desevaux
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D002415:Cats; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007472:Iohexol / Q000378:metabolism; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D011897:Random Allocation
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001552:Benzazepines; D010648:Phenylacetates; D007472:Iohexol; D004159:Diphenylamine; C044946:benazepril; C551524:robenacoxib
keywords: ACE inhibitor; Benazepril; Cat; Glomerular filtration; NSAID; Robenacoxib; Safety