Pharmacology of ifosfamide
Pharmacology of ifosfamide
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DOI：
10.1159/000073350
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发表时间：
2003-01-01
期刊：
影响因子：
3.5
通讯作者：
Franceschi, L
中科院分区：
文献类型：
--
作者：
Furlanut, M;Franceschi, L
异环磷酰胺是一种双官能团烷基化试剂，通过静脉途径作为外消旋混合物用于治疗各种肿瘤。它是一种恶氮磷衍生物，其结构式类似于环磷酰胺。作为一种前药，它需要在肝脏中通过细胞色素混合功能的氧化酶系统激活。在各种代谢物中，异福酰胺芥末可能是最重要的细胞毒性化合物，能够在DNA链之间产生不可修复的交联。耐药性是由于肿瘤细胞修复DNA损伤的能力所致。丙烯醛可能导致出血性膀胱炎，而氯乙醛可能与肾脏和神经毒性有关。硫醇供体(MESNA)可以预防尿毒效应，但不能预防肾脏和神经毒性。药物动力学明显受给药途径和疗程、年龄、联合用药、肝肾功能的影响。版权所有(C)2003 S.Karger AG，巴塞尔。
Ifosfamide is a bifunctional alkylating agent, used as a racemic mixture by intravenous route in the treatment of various tumors. It is an oxazaphosphorine derivative with a structural formula similar to that of cyclophosphamide. As a prodrug it requires activation in the liver by a cytochrome mixed-function oxidase system. Among various metabolites, ifosforamide mustard probably represents the most important cytotoxic compound able to produce irreparable cross-links between DNA strands. Resistance is due to the ability of neoplastic cells to repair DNA damages. Acrolein may induce hemorrhagic cystitis, whereas chloroacetaldehyde may be responsible both for nephro- and neurotoxicity. A thiol donor (mesna) can prevent urotoxic effects but not nephro- and neurotoxicity. Pharmacokinetics is markedly influenced by route of administration and duration of treatment, age, co-medication, liver and renal function. Copyright (C) 2003 S. Karger AG, Basel.