A comparative study on the adverse effects of flunixin, ketoprofen and phenylbutazone in miniature donkeys: Haematological, biochemical and pathological findings

Abstract

AIM: To evaluate the adverse effects of flunixin, ketoprofen and phenylbutazone when administered I/V to clinically normal miniature donkeys. METHODS: Twenty clinically normal adult (2.0–2.5 years old) male miniature donkeys weighing 113–136 kg and 0.81–0.86 m tall were randomly assigned to one of four groups, and administered either saline (n=5), 1.0 mg/kg flunixin (n=5), 2.2 mg/kg ketoprofen (n=5), or 4.4 mg/kg phenylbutazone (n=5) I/V at 0800 hours on Day 1, then every 12 h, for 12 days. The animals were observed every 8 h, and examined physically daily. Blood, faeces and urine samples were collected daily from all donkeys, for haematological indices and enzyme activities, occult blood, and urinalysis, respectively. Immediately after euthanasia, complete post-mortem examinations were performed on all donkeys, and gross lesions recorded. Histopathology was conducted on a wide range of tissues. RESULTS: Clinically, mild anorexia and diarrhoea were observed during the study only in donkeys treated with phenylbutazone. There was an effect of treatment with the non-steroidal anti-inflammatory drugs (NSAID) on red blood cell (RBC) counts, packed cell volume (PCV) and enzyme activities, but not on urine. Lesions were observed in the glandular mucosa of the stomach of all donkeys treated with NSAID, including ulceration in most. Also, in donkeys treated with NSAID, hyperaemia, erosion and ulceration of the gastrointestinal tract, and congestion of the liver, kidney and spleen, were observed. Microscopically, hepatic and renal lesions comprised biliary hyperplasia and interstitial nephritis, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The gastrointestinal, hepatic and renal lesions observed in the donkeys treated with NSAID demonstrated the toxic potential of NSAID, which was greatest for animals treated with phenylbutazone, less for flunixin, and least for ketoprofen. When use of these compounds is contemplated in clinical cases, the risk of adverse effects and the comparative toxic potential should be considered, together with the efficacy of the compound for the condition being treated.