Pharmacokinetic disposition of the oral iron chelator deferiprone in the domestic pigeon (Columba livia).
Deferiprone is a bidentate oral iron chelator used for the treatment of iron overload in people. The purpose of this study was to determine the pharmacokinetic disposition of deferiprone in the domestic pigeon (Columba livia) and to compare the results with a previous study in the white leghorn chicken. Deferiprone (DFP) was administered orally as a suspension at a single dose of 50 mg/kg to 10 iron-loaded (IL-DFP) pigeons and 10 non--iron-loaded controls (NIL-DFP). Six NIL-DFP birds were also administered deferiprone intravenously to determine the bioavailability of the drug after a 30-day washout period. To evaluate if deferiprone induces its own metabolism, the pharmacokinetic disposition of the drug was also studied in the IL-DFP group after oral therapy with deferiprone at a dosage of 50 mg/kg q12h for 30 days. For each phase, collected blood was analyzed for deferiprone by high-performance liquid chromatography to develop a plasma concentration versus time curve. Deferiprone was rapidly absorbed from the gastrointestinal tract, with plasma concentrations effective for iron chelation maintained for at least 8 hours after administration in iron-loaded birds. The half-life (mean +/- SD) for deferiprone given orally to the IL-DFP and NIL-DFP groups was 2.98 +/- 0.85 hours and 3.26 +/- 1.25 hours, respectively, and when intravenously administered was 3.79 +/- 1.23 hours. The half-life after 30 days of treatment was 3.42 +/- 1.18 hours. Oral bioavailability was 44%. This study demonstrated that oral absorption of deferiprone is acceptable, it does not induce its own metabolism, and the drug was widely distributed in the pigeon, as it was in the chicken, with a longer half-life than that reported in mammals. Minor interspecies variations in the pharmacokinetics of deferiprone exist between chickens and pigeons.
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; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D010856:Columbidae / Q000097:blood; D018592:Cross-Over Studies; D000077543:Deferiprone; D005260:Female; D006207:Half-Life; 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*; D008297:Male; 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