Pharmacokinetic Disposition of the Oral Iron Chelator Deferiprone in the White Leghorn Chicken

Abstract

Deferiprone is a bidentate oral iron chelator used for the treatment of transfusional iron overload in people. The purpose of this study was to determine the pharmacokinetic disposition of deferiprone in the white leghorn chicken as a potential model upon which to base therapeutic regimens for the treatment of iron storage disease (hemochromatosis) in affected avian species. A suspension of deferiprone (DFP) was administered orally at a single dose of 50 mg/kg to 10 birds that were iron-loaded (IL-DFP) and 10 non--iron-loaded control birds (NIL-DFP). After a 30-day washout period, 5 birds from the NIL-DFP group were used for a bioavailability study of deferiprone administered intravenously at the same dose. Blood samples were collected at varying intervals over a 24-hour period and were analyzed for deferiprone by high-performance liquid chromatography, then plasma concentration versus time curves were developed. Deferiprone was rapidly absorbed from the gastrointestinal tract of the chicken, with plasma concentrations effective for iron chelation in humans (>20 micromol/L) maintained for at least 8 hours after oral dosing. The half-life (mean +/- SD) of the orally administered deferiprone in the IL-DFP and NIL-DFP groups was 2.91 +/- 0.78 hours and 3.61 +/- 0.90 hours, respectively, and was 2.42 +/- 0.24 hours for deferiprone administered intravenously. The mean oral bioavailability was 93%. Deferiprone is well absorbed and widely distributed in the chicken, with a longer half-life than reported in mammals.

Hemocromatose e capilariose em tucano-de-bico-verde (Ramphastos dicolorus)

“…Outro tratamento comumente citado em literatura é a remoção do ferro por meio de flebotomias semanais que forçam o organismo a utilizar o ferro acumulado para as funções fisiológicas (Brown, 2010;Grespan & Raso, 2014;Harcourt-brown, 2010). O procedimento é estressante e pode causar anemias secundárias, sendo retirado em sangue cerca de 1% do peso da ave por semana, sendo que o uso de quelantes é outra alternativa para a mobilização do ferro depositado (Brown, 2010;Cork, 2000;Cubas, 2008;Harcourt-brown, 2010;Whiteside, 2001).…”

“…Exames radiológicos e ultrassonográficos não invasivos podem fornecer informações úteis, indicando hepatomegalia, cardiomegalia e ascite (Whiteside, 2001). Exames hematológicos e testes de bioquímica sérica apresentam limitado valor no diagnóstico, pois nem sempre se elevam.…”

Use of deferiprone for the treatment of hepatic iron storage disease in three hornbills

“…16,17 However, both methods require repeated handling of the bird for bleeding or SC injections; therefore, the use of an orally administered chelator would make treatment considerably easier. Oral administration of deferiprone, which leads to increased iron excretion via feces, has been evaluated in chickens and pigeons [21][22][23] but not in exotic pet birds.…”

“…Deferiprone was administered to the hornbills in the present report at a dosage of 75 mg/kg once daily over a treatment period of 3 months. This dosage was based on the practical aspect of only being able to administer a dosage once daily, on the results of studies on the pharmacokinetic disposition of deferiprone in domestic pigeons 22 and the white leghorn chicken, 23 and on the clinical experience of the authors of those studies, 22,23 who have witnessed clinical improvement in affected exotic avian species treated with 75 mg/kg once daily. p Deferiprone is well absorbed and widely distributed in chickens and domestic pigeons, with a longer half-life than that reported in mammals.…”

“…In chickens and domestic pigeons, the oral administration of deferiprone at a dose of 50 mg/kg (22.7 mg/lb) achieved plasma concentrations suitable for effective iron chelation treatment for at least 8 hours. 22,23 Although deferiprone is licensed for use in human patients in Europe, it is not currently licensed for use in human or veterinary patients in the United States or Canada. However, under the Compassionate Use Program, 28 deferiprone may be requested from the manufacturer on a case-bycase basis.…”