Apparent tolerance of turkey vultures (Cathartes aura) to the non‐steroidal anti‐inflammatory drug diclofenac

Abstract

The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose -0.1-0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

The Pied Crow (Corvus Albus) Is Insensitive to Diclofenac at Concentrations Present in Carrion

“…In addition, these vultures always demonstrated massive increases in serum uric acid concentrations with concurrent visceral gout evident on necropsy. Our findings were, however, very similar to those previously reported for Turkey Vultures (Rattner et al, 2008), suggesting that toxicity is not linked to consumption of carrion (and consequential to high uric acid generation) but to other biochemical factors.…”

“…The pharmacokinetic parameters (in comparison to other avian species) demonstrated a clear relationship between half-life and death/toxicity (Table 3; Swan et al, 2006b;Naidoo et al, 2007Naidoo et al, , 2009Rattner et al, 2008). In all cases where plasma concentration data were available, birds tended to die when half-life elimination was above 12 hr.…”

“…In the Pied Crow, diclofenac was characterized by a rapid half-life elimination, which was much shorter than that observed in Turkey Vultures and Gyps spp. (Swan et al, 2006b;Rattner et al, 2008;Naidoo et al, 2009). The half-life elimination was, however, twice that reported for the Domestic Chicken (as evaluated in a full pharmacokinetic study), which also survived with no signs of toxicity.…”

“…The single resultant profile was then evaluated using standard equations and a noncompartmental model. To allow comparisons with other bird species, the noncompartmental equations were also fitted to previously published data (Rattner et al, 2008) for Turkey Vultures (Cathartes aura; n54) dosed at either 8 or 25 mg/kg body weight and to sparse data previously presented for a chicken that died when dosed at 5 mg/kg (intramuscular administration; Naidoo et al, 2007;Rattner et al, 2008).…”

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism

“…Further, controlled toxicity studies have now shown that diclofenac is also toxic to three other Gyps vulture species (G. africanus, G. coprotheres and G. fulvus) as well as the domestic chicken (Gallus gallus), although at a higher dose for the latter (Swan et al 2006b;Naidoo et al 2007. At the same time, it has been clearly shown to be safe at very high doses in Turkey vultures (Cathartes aura) (Rattner et al 2008) and in House crow (Corvus albus; unpublished work). Hence, very signiWcant diVerences in toxicity between diVerent bird species clearly exist.…”