Barman Balfour J A, Foster R H
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 1999 Sep;58(3):553-78. doi: 10.2165/00003495-199958030-00021.
Patients with beta-thalassaemia and other transfusion-dependent diseases develop iron overload from chronic blood transfusions and require regular iron chelation to prevent potentially fatal iron-related complications. The only iron chelator currently widely available is deferoxamine, which is expensive and requires prolonged subcutaneous infusion 3 to 7 times per week or daily intramuscular injections. Moreover, some patients are unable to tolerate deferoxamine and compliance with the drug is poor in many patients. Deferiprone is the most extensively studied oral iron chelator to date. Non-comparative clinical studies mostly in patients with beta-thalassaemia have demonstrated that deferiprone 75 to 100 mg/kg/day can reduce iron burden in regularly transfused iron-overloaded patients. Serum ferritin levels are generally reduced in patients with very high pretreatment levels and are frequently maintained within an acceptable range in those who are already adequately chelated. Deferiprone is not effective in all patients (some of whom show increases in serum ferritin and/or liver iron content, particularly during long term therapy). This may reflect factors such as suboptimal dosage and/or severe degree of iron overload at baseline in some instances. Although few long term comparative data are available, deferiprone at the recommended dosage of 75 mg/kg/day appears to be less effective than deferoxamine; however, compliance is superior with deferiprone, which may partly compensate for this. Deferiprone has additive, or possibly synergistic, effects on iron excretion when combined with deferoxamine. The optimum dosage and long term efficacy of deferiprone, and its effects on survival and progression of iron-related organ damage, remain to be established. The most important adverse effects in deferiprone-treated patients are arthropathy and neutropenia/agranulocytosis. Other adverse events include gastrointestinal disturbances, ALT elevation, development of antinuclear antibodies and zinc deficiency. With deferiprone, adverse effects occur mostly in heavily iron-loaded patients, whereas with deferoxamine adverse effects occur predominantly when body iron burden is lower.
Deferiprone is the most promising oral iron chelator under development at present. Further studies are required to determine the best way to use this new drug. Although it appears to be less effective than deferoxamine at the recommended dosage and there are concerns regarding its tolerability, it may nevertheless offer a therapeutic alternative in the management of patients unable or unwilling to receive the latter drug. Deferipone also shows promise as an adjunct to deferoxamine therapy in patients with insufficient response and may prove useful as a maintenance treatment to interpose between treatments.
β地中海贫血及其他依赖输血的疾病患者，因长期输血会出现铁过载，需要定期进行铁螯合治疗以预防可能致命的铁相关并发症。目前唯一广泛可用的铁螯合剂是去铁胺，它价格昂贵，需要每周进行3至7次长时间的皮下输注或每日进行肌肉注射。此外，一些患者无法耐受去铁胺，许多患者对该药物的依从性较差。去铁酮是迄今为止研究最广泛的口服铁螯合剂。大多针对β地中海贫血患者的非对照临床研究表明，去铁酮75至100毫克/千克/天可降低定期输血的铁过载患者的铁负荷。预处理水平非常高的患者血清铁蛋白水平通常会降低，而在那些已经得到充分螯合的患者中，血清铁蛋白水平通常能维持在可接受范围内。去铁酮并非对所有患者都有效（其中一些患者血清铁蛋白和/或肝脏铁含量会升高，尤其是在长期治疗期间）。这可能反映了一些因素，比如在某些情况下剂量欠佳和/或基线时铁过载程度严重。尽管目前可获得的长期对比数据较少，但去铁酮以75毫克/千克/天的推荐剂量使用时似乎比去铁胺效果差；然而，去铁酮的依从性更好，这可能在一定程度上弥补了这一不足。去铁酮与去铁胺联合使用时对铁排泄有相加或可能协同的作用。去铁酮的最佳剂量、长期疗效及其对铁相关器官损伤的存活和进展的影响仍有待确定。接受去铁酮治疗的患者最重要的不良反应是关节病和中性粒细胞减少症/粒细胞缺乏症。其他不良事件包括胃肠道不适、谷丙转氨酶升高、抗核抗体产生和锌缺乏。使用去铁酮时，不良反应大多发生在铁负荷重的患者中，而使用去铁胺时，不良反应主要发生在机体铁负荷较低时。
去铁酮是目前正在研发的最有前景的口服铁螯合剂。需要进一步研究以确定使用这种新药的最佳方法。尽管其在推荐剂量下似乎比去铁胺效果差，且对其耐受性存在担忧，但它仍可能为无法或不愿接受后者治疗的患者提供一种治疗选择。去铁酮作为去铁胺治疗反应不足患者的辅助药物也显示出前景，并且可能被证明是在治疗间隔期进行维持治疗的有用药物。
