Abstract:
In a safety study, Cape GriVon vultures (Gyps
coprotheres) were dosed with ketoprofen at single doses of
~1 mg/kg (n = 5) and 5 mg/kg (n = 11). No toxicity was
reported in the 1 mg/kg group, with the AUCinf, Vz and Cl
being 10.42 g/ml h, 0.37 l/kg and 0.10 l/h kg, respectively.
Toxicity occurred in the 5 mg/kg group, with 7 of
the 11 birds dying. Clinical signs of toxicity included
depression, loss of appetite and apparent coma. Animals
died within 48 h of dosing. The AUCinf, Vz and Cl in the
birds that survived were 52.26 g/ml h, 0.45 l/kg and
0.10 l/h kg, respectively. The AUCinf, Vz and Cl in the birds
those died were 207.90 g/ml h, 0.26 l/kg and 0.02 l/h kg,
respectively. Based on the increase in the AUCinf and Cmax
in the birds that died, we surmise that toxicity resulted from
saturation of the metabolic process. While the exact
metabolic pathway remains unknown in these vultures, we
believe that toxicity may be due to pharmacogenomic
diVerences in the cytochrome P450 pathway.
