氨磷汀的潜力:从细胞保护剂到治疗剂。

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桑蒂尼V，贾尔斯FJ

氨磷汀的潜力:从细胞保护剂到治疗剂。

《血液学报》1999年11月;84(11):1035-42。

PubMed ID

10553165 (PubMed视图

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摘要

背景与目的:氨磷汀是一种无机硫代磷酸盐细胞保护剂，化学名称为乙硫醇，2-[(3-氨基丙基)氨基]磷酸二氢。它是一种游离硫醇的前药，可作为暴露于细胞毒性药物的组织中产生的自由基的清道夫，并与此类药物的活性代谢物结合。阿米弗汀最初是在一个机密的核战争项目中作为一种辐射保护剂开发的。在该项目解密后，它被评估为一种细胞保护剂，对抗烷基化药物和顺铂的毒性。事实上，在晚期和转移性实体肿瘤患者中，氨磷汀的预处理耐受性良好，减少了顺铂、环磷酰胺和长春碱治疗相关的累积血液学、肾脏和神经毒性。本综述的目的是集中讨论阿米福汀作为一种骨髓保护和细胞保护药物在化疗治疗中的重要性，介绍最新的结果，并讨论阿米福汀在骨髓增生异常综合征治疗中的应用。证据和信息来源:本研究中分析的材料包括作者以全文或临床方案的形式发表或正在发表的数据。发表在Medline覆盖的期刊上的文章和摘要构成了另一个信息来源。现状和前景:阿米弗汀，以前被称为WR-2721，是一种有机硫代磷酸盐，被开发用于选择性地保护正常组织免受化疗和放疗的毒性。氨磷汀是一种在组织部位通过碱性磷酸酶去磷酸化为其活性代谢物的前药。 Differences in the alkaline phosphatase concentrations of normal versus tumor tissues can result in greater conversion of amifostine in normal tissues. Once inside the cell the free thiol provides an alternative target to DNA and RNA for the reactive molecules of alkylating or platinum agents and acts as a potent scavenger of the oxygen free radicals induced by ionizing radiation and some chemotherapies. Preclinical animal studies demonstrated that the administration of amifostine protected against a variety of chemotherapy-related toxicities including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity, cyclophosphamide- and bleomycin-induced pulmonary toxicity, and the cytotoxicities (including cardiotoxicity) induced by doxorubicin and related chemotherapeutic agents. Amifostine was shown to protect a variety of animal species from lethal doses of radiation. Studies in tumor-bearing animals demonstrated that the administration of amifostine results in cytoprotection without loss of antitumor activity. Multiple phase I studies were carried out with amifostine in combination with chemotherapy for various neoplasms. Appropriate doses of amifostine resulted to be 740-910 mg/m(2) in a single dose regimen, and 340 mg/m(2) in a multiple dose regimen. Amifostine afforded not only hematologic protection, but also other organ protection from cytotoxic agents such as nephrotoxicity, mucositis and peripheral neuropathy from cisplatin. Many studies have been performed to investigate cytoprotective efficacy of amifostine. In brief, amifostine gives hematologic protection from cyclophosphamide, carboplatin, mitomycin C, fotemustine and radiotherapy; renal and peripheral nerve protection from cisplatin; mucosa, skin, and salivary gland from radiotherapy. In phase I/II studies these properties have been confirmed, together with a generally good tolerability of the drug, hypotension being the most common side effect. It has been observed that amifostine possibly enhances the anti-tumor effect of carboplatin, nitrogen mustard, melphalan, and cisplatin combined with 5-FU or vinblastine. For all these characteristics, amifostine is at present broadly used as supportive treatment during chemotherapy, in lymphomas and solid tumors, and its spec

引用本文的药物库数据

药物

Amifostine

药物靶点

药物	目标	种类	生物	药理作用	行动
Amifostine	碱性磷酸酶，胎盘样	蛋白质	人类	是的	诱导物	细节