Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

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.

Repeated oral dose tolerance in dogs treated concomitantly with ciclosporin and oclacitinib for three weeks.

BACKGROUND: Ciclosporin and oclacitinib are immunomodulators approved for the treatment of canine atopic dermatitis. The administration of a short course of prednisolone at the beginning of ciclosporin therapy hastens the efficacy of this drug; oclacitinib has a rapid antipruritic effect similar to that of prednisolone. OBJECTIVES: To evaluate the oral tolerance of oclacitinib and ciclosporin given concurrently for three weeks. ANIMALS: Two groups of eight beagles. METHODS: Dogs were randomized to receive oclacitinib alone (0.4-0.6 mg/kg twice daily for 14 days then once daily for seven days) or in combination with ciclosporin (5 mg/kg once daily) for three weeks. They were examined every day and adverse events were recorded. Blood samples were collected during the acclimatization phase, weekly during treatment and at the end of the study for haematology, clinical chemistry and coagulation evaluation. RESULTS: There were no abnormal clinical observations following treatment with oclacitinib given alone or concomitantly with ciclosporin, with the exception of diarrhoea in two dogs receiving both drugs. Three dogs from each group experienced transient inappetence; three dogs treated with oclacitinib had mild weight loss. Clinical pathology parameters remained within the reference range for beagle dogs at that facility. CONCLUSIONS AND CLINICAL IMPORTANCE: The concomitant administration of ciclosporin and oclacitinib for three weeks to beagles was well tolerated and was not associated with an increase in the number of adverse events or laboratory abnormalities beyond those associated with oclacitinib given alone.