The safety and pharmacokinetics of carprofen, flunixin and phenylbutazone in the Cape Vulture (Gyps coprotheres) following oral exposure
Loading...
Date
Authors
Fourie, Tamsyn Ann
Cromarty, Allan Duncan
Duncan, N.M. (Neil)
Wolter, Kerri
Naidoo, Vinny
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
The following study evaluates the overt toxic potential of carprofen (CRP), flunixin (FXN)
and phenylbutazone (PBZ) in Old world vultures in relation to historic toxicity data for diclofenac
and ketoprofen, with the Cape vulture (Gyps coprotheres) being the indicator species.
The toxic potential of a single oral dose of CRP (11.5 mg/kg), FXN (1 mg/kg),PBZ (1.7 mg/
kg) or water was evaluated by means of a four-way parallel study (n = 2), as means of ascertaining
if these drugs were as toxic as diclofenac in the vulture. No unscheduled deaths or
pathological lesions were noted following exposure. Clinical signs of lethargy and depression
were, however, noted in one CRP, two FXN and one PBZ treated birds. Mild reversible
inhibition of UA excretion was evident in all three groups, although UA remained within the
population reference interval in contrast to the effects previously described for diclofenac
and ketoprofen. All treatment groups had a drug concentration responsive increase in alanine
transferase activity. CRP, FXN and PBZ were characterised by a maximum plasma
concentration (Cmax) of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/
ml at 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours (Tmax) respectively and a half-life of elimination
of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. While we could not demonstrate a
lethal effect of the tested substances, the presence of toxic clinical signs, clinical pathological
changes and/or long half-lives of elimination suggests that all three drugs have a potential
for toxicity in a larger population or on repeat administration. In conclusion while the
studied substances were not as overtly toxic as diclofenac, they are of safety concern.
Description
Keywords
Carprofen (CRP), Flunixin (FXN), Phenylbutazone (PBZ), Cape vulture (Gyps coprotheres)
Sustainable Development Goals
Citation
Fourie T, Cromarty D, Duncan N, Wolter K, Naidoo V (2015) The Safety and Pharmacokinetics of Carprofen, Flunixin and Phenylbutazone in the Cape Vulture (Gyps coprotheres) following Oral Exposure. PLoS ONE 10(10): e0141419. DOI: 10.1371/journal.pone.0141419.