Supot RodratPavena YamanontJeeranut TankanitlertUdom ChantraraksriSuthat FucharoenNoppawan Phumala MoralesMahidol UniversityPharmongkutklao College of Medicine2018-06-112018-06-112012-08-01Pharmacology. Vol.90, No.1-2 (2012), 88-9414230313003170122-s2.0-84863091147https://repository.li.mahidol.ac.th/handle/20.500.14594/15159Dose-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. Copyright © 2012 S. Karger AG, Basel.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1159/000339658