Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Pharmacology. 2012;90(1-2):88-94. doi: 10.1159/000339658. Epub 2012 Jul 2.
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.
口服铁螯合剂地拉罗司（L1）的剂量相关药代动力学和尿铁排泄（UIE）在 12 例严重β-地中海贫血/血红蛋白 E 患者中进行了研究。这些患者接受了两次 25 和 50mg/kg 的单剂量治疗，间隔 2 周洗脱期。地拉罗司吸收迅速，给药后 1 小时内达到最大浓度（C(max)）。药代动力学参数包括 C(max)和从零时到无穷大的浓度时间曲线下面积（AUC(0-∞)）以及非结合和葡萄糖醛酸结合的地拉罗司（L1 和 L1-G）的尿排泄均与地拉罗司的剂量成正比。L1-G 与 L1 的 AUC(0-∞)比值和 L1-G 的尿排泄百分比表明，增加剂量不会影响地拉罗司的生物转化。高剂量时观察到 L1 的终末消除半衰期更长和分布容积更高，这与血清中的地拉罗司螯合铁有关。出乎意料的是，UIE 与地拉罗司剂量的增加没有显示出线性关系。UIE 与肌酐清除率之间的相关性表明，在接受高剂量地拉罗司治疗的肾功能损害患者中，L1-铁复合物可能重新分布。
