The safety of carprofen, flunixin and phenylbutazone in the Cape Vulture (Gyps coprotheres) – a pilot study

Abstract

The safety of a single oral dose of carprofen (11.5 mg/kg), flunixin (1 mg/kg) and phenylbutazone (1.7 mg/kg) was evaluated in the Cape Vulture (Gyps coprotheres) by means of a four-way parallel study, using two birds per treatment. Clinical observations, clinical pathology and necropsy examinations were determining factors. Clinical signs of lethargy and depression were noted in one of the carprofen (CRP), two of the flunixin (FXN) and one of the phenylbutazone (PBZ) treated birds. Serum alanine transferase (ALT), albumin, sodium, calcium, potassium and uric acid (UA) concentrations were monitored up to 48 hours post dosing. Mild reversible inhibition of UA excretion was evident in all three groups, although UA remained within population reference intervals. All treatment groups had a drug concentration responsive ALT increase. No pathological lesions where noted on histopathology. Oral absorption of CRP, FXN and PBZ was characterised by a maximum plasma concentration of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/ml obtained in 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours respectively and a half-life of elimination of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. The volume of distribution was 13.62 ± 9.91 L/kg (CRP); 3.29± 0.75 L/kg (FXN) and 0.13 ± 0.03 L/kg (PBZ). Area under the curve until the last time point was 21.72± 20.10; 0.78± 0.28 and 263.35 ±68.69 μg/mL*h for CRP, FXN and PBZ respectively. Glucuronidation was identified in FXN and CRP treated birds. The long half-life of PBZ and CRP creates concern that accumulative toxicity may occur. Both FXN and PBZ are potentially hepatotoxic indicating that clinical use or the presence thereof in the food-chain should be avoided. CRP may be of clinical benefit in the vulture, but only as a single treatment. This drug should also be safe in the case of possible contamination of the food chain, as it is unlikely that vultures will be exposed to the drug often enough for it to be cumulative