The pharmacokinetics of tolfenamic acid in Himalayan Griffon vultures. A better understanding for the safety of the drug in old world vultures.

The pharmacokinetics of tolfenamic acid (TA) was determined for Himalayan Griffon vultures from published data. The evaluation included 38 birds dosed orally at 3.2-3.7 mg/kg, of which 2 unscheduled deaths were recorded. The maximum concentration, time to maximum concentration, clearance and elimination half-life were 5.67 ± 3.24 µg/ml, 2.11 ± 0.67 h, 0.11 ± 0.08 L/h*kg and 12.04 ± 7.51 h, respectively. Drug elimination was comparable to diclofenac (DF), a toxic non-steroidal anti-inflammatory drug, which was unexpected given TA's safety in vultures. Subsequent uric acid (UA) evaluations showed that the increase in UA from TA was less extensive and more reversible than DF. Given the more limited changes in UA, toxicity appears to resulted from altered renal perfusion, a known side effect of TA, rather than UA transporter inhibition as seen with DF. This would likely explain why the long T1/2 did not result in more substantial toxicity.