Pharmacokinetic disposition of the oral iron chelator deferiprone in the white leghorn chicken.
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.
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Douglas P
DP
Whiteside
Ian K
IK
Barker
Peter D
PD
Conlon
Angelo
A
Tesoro
Jake J
JJ
Thiessen
Kay G
KG
Mehren
Robert M
RM
Jacobs
Michael
M
Spino
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002645:Chickens / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D000077543:Deferiprone; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D007408:Intestinal Absorption / Q000187:drug effects; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019190:Iron Overload / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D011201:Poultry Diseases / Q000188:drug therapy* / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013045:Species Specificity; D016896:Treatment Outcome
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone