Removing the Threat of Diclofenac to Critically Endangered Asian Vultures

Veterinary use of the nonsteroidal anti-inflammatory (NSAID) drug diclofenac in South Asia has resulted in the collapse of populations of three vulture species of the genusGyps to the most severe category of global extinction risk. Vultures are exposed to diclofenac when scavenging on livestock treated with the drug shortly before death. Diclofenac causes kidney damage, increased serum uric acid concentrations, visceral gout, and death. Concern about this issue led the Indian Government to announce its intention to ban the veterinary use of diclofenac by September 2005. Implementation of a ban is still in progress late in 2005, and to facilitate this we sought potential alternative NSAIDs by obtaining information from captive bird collections worldwide. We found that the NSAID meloxicam had been administered to 35 captiveGyps vultures with no apparent ill effects. We then undertook a phased programme of safety testing of meloxicam on the African white-backed vultureGyps africanus, which we had previously established to be as susceptible to diclofenac poisoning as the endangered AsianGyps vultures. We estimated the likely maximum level of exposure (MLE) of wild vultures and dosed birds by gavage (oral administration) with increasing quantities of the drug until the likely MLE was exceeded in a sample of 40G. africanus. Subsequently, sixG. africanus were fed tissues from cattle which had been treated with a higher than standard veterinary course of meloxicam prior to death. In the final phase, ten Asian vultures of two of the endangered species(Gyps bengalensis,Gyps indicus) were dosed with meloxicam by gavage; five of them at more than the likely MLE dosage. All meloxicam-treated birds survived all treatments, and none suffered any obvious clinical effects. Serum uric acid concentrations remained within the normal limits throughout, and were significantly lower than those from birds treated with diclofenac in other studies. We conclude that meloxicam is of low toxicity toGyps vultures and that its use in place of diclofenac would reduce vulture mortality substantially in the Indian subcontinent. Meloxicam is already available for veterinary use in India

Effect of Administration of Meloxicam and Diclofenac by Gavage on Uric Acid in the Serum of Vultures

<p>Blue symbols show the ratio of the geometric mean serum concentration of uric acid for a group ofGyps africanus treated with meloxicam by gavage to that for a control group treated with water and sampled at the same time. Vertical lines show 95% confidence limits for the ratio. The dashed horizontal line indicates a ratio of 1; i.e., no effect of treatment. For each of six samplings after treatment, results are shown for experiments in which different doses of drug were used. The fill colour of the blue symbols indicates the meloxicam dose for the treated group: white = 0.5 mg kg⁻¹ (Phase I); light blue = 1.0 mg kg⁻¹ (Phase II); dark blue = 2.0 mg kg⁻¹ (squares = Phase III, diamonds = Phase IV-2). Red vertical bars show the maximum and minimum values of the equivalent ratio for two groups of<i>G. africanus,</i> one group treated with 0.8 mg kg⁻¹ of diclofenac by gavage and another group treated with water and sampled at the same time. Open red symbols show the ratio of the serum concentration after treatment to that at the time of treatment for three individualG. fulvus given 0.8 mg kg⁻¹ of diclofenac by gavage. Filled red symbols show the ratio of the serum concentration 24 h post-treatment to that 1 h post-treatment for three individualG. bengalensis given 0.25 mg kg⁻¹ (squares) and 2.5 mg kg⁻¹ (diamond) of diclofenac by gavage. Data from diclofenac experiments were taken from references [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040066#pbio-0040066-b001" target="_blank">1</a>] and [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040066#pbio-0040066-b007" target="_blank">7</a>].</p

Relationship of Uric Acid in Serum to the Dose of Meloxicam and Diclofenac Administered and to the Administration Method

<p>Serum concentration of uric acid inGyps africanus 48 h (turquoise) and 96 h (blue) after treatment, in relation to the dose of meloxicam administered per kg of vulture body weight. For comparison, the geometric mean uric acid level (central horizontal line) and 95% range (upper and lower horizontal lines) of the experimental birds 24 h before treatment are shown. Also shown are serum concentrations of uric acid 24 h after treatment inG. africanus (red squares),G. bengalensis (red diamonds), andG. fulvus (red triangles), to which diclofenac was administered by various methods. The red line shows the regression model fitted to these data. Panels show results for different methods of administration of meloxicam to<i>G. africanus:</i> (A) gavage, (B) by feeding liver from meloxicam treated cattle, (C) by feeding muscle from meloxicam-treated cattle. Data from diclofenac experiments were taken from references [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040066#pbio-0040066-b001" target="_blank">1</a>] and [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040066#pbio-0040066-b007" target="_blank">7</a>].</p