title: Comparison of pharmacokinetics and urinary iron excretion of two single doses of deferiprone in β-thalassemia/hemoglobin E patients.
abstract: Dose-related pharmacokinetics and urinary iron excretion (UIE) of an orally active iron chelator, deferiprone (L1), was investigated in 12 severe β-thalassemia/hemoglobin E patients. The patients received two single doses of 25 and 50 mg/kg with a 2-week washout period. Deferiprone was rapidly absorbed and reached maximum concentration (C(max)) within 1 h after administration. Pharmacokinetic parameters including C(max) and area under concentration time curve from time zero to infinity (AUC(0-∞)) as well as urinary excretion of non-conjugated and glucuronide-conjugated deferiprone (L1 and L1-G) increased proportionally with the dose of deferiprone. A constant ratio of AUC(0-∞) of L1-G to L1 and a percentage of urinary excretion of L1-G indicated that increasing the dosage does not influence deferiprone biotransformation. Longer terminal elimination half-lifeand higher volume of distribution of L1 were observed with the high dose and correlated with deferiprone-chelated iron in serum. Unexpectedly, UIE did not show a linear relationship with the increased dose of deferiprone. The correlation between UIE and creatinine clearance suggested the possibility of L1-iron complex redistribution in patients with renal impairment treated with high-dose deferiprone.
authors: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors: Supot
authors: S
authors: Rodrat
authors: Pavena
authors: P
authors: Yamanont
authors: Jeeranut
authors: J
authors: Tankanitlert
authors: Udom
authors: U
authors: Chantraraksri
authors: Suthat
authors: S
authors: Fucharoen
authors: Noppawan Phumala
authors: NP
authors: Morales
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D000077543:Deferiprone; D005260:Female; D020719:Glucuronides / Q000652:urine; D006446:Hemoglobin E; D006801:Humans; D007501:Iron / Q000652:urine*; D007502:Iron Chelating Agents / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011728:Pyridones / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult; D017086:beta-Thalassemia / Q000652:urine*
chemical_list: D020719:Glucuronides; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D006446:Hemoglobin E; D007501:Iron