骨肉瘤化疗课件.pptVIP

Private Confidential - For Internal Use Only  骨肉瘤化疗--HAM 骨肉瘤化疗药物简述 异环磷酰胺--------H oloxan 多柔比星----------A dm 大剂量甲氨蝶呤--- M tx 骨肉瘤治疗策略简述 诺凡麦公司肿瘤业务部致力骨及软组织肉瘤领域 异环磷酰胺 异环磷酰胺的作用机制（1） Ifosfamide is a cytotoxic agent belonging to the group of the oxazaphosphorines. 异环磷酰胺是氧氮磷环类细胞毒药物。 Chemically related to Nitrogen mustard, ifosfamide is a synthetic analogue of cyclophosphamide. 异环磷酰胺是环磷酰胺的同分异构体。 Ifosfamide is inactive in vitro and activated in vivo (preferably) in the liver by the microsomal cytochrome mixed-function oxidase system (Cytochrome P450 system) to 4-hydroxy-ifosfamide. 体外异环磷酰胺没有活性，体内经过P450酶系统活化后生成活性代谢物。 异环磷酰胺的作用机制（2） The cytotoxic effect of ifosfamide is due to interaction between isophosphoramide mustard and the DNA. The alkylation results in strand breaks and cross-linking of the DNA. 异环磷酰胺的代谢活性产物与DNA产生交联，阻止细胞复制。 Acrolein is blamed for the urotoxic side effects of ifosfamide. 异环磷酰胺代谢产物—丙烯醛是引起泌尿道毒性的原因。 异环磷酰胺的药物动力学（1） Ifosfamide is detectable in organs and tissues within a few minutes after i.v. administration. 静脉使用异环磷酰胺数分钟后便可在器官及组织中检测到。 There is linear relationship between the plasma concentrations reached and administered dose of ifosfamide. 异环磷酰胺的血浆浓度与其剂量呈线性关系。 The serum half-life of ifosfamide lies between 4 and 7 hours following i.v. administration. 静脉使用异环磷酰胺后，其半衰期是4至7小时。 Ifosfamide (and its metabolites) are able to cross the blood-brain barrier. 异环磷酰胺及其代谢产物可通过血脑屏障。 There exist no confirmed data that ifosfamide crosses the placenta. 目前没有可靠证据证明异环磷酰胺可通过胎盘。 异环磷酰胺的药物动力学（2） There is no confirmed data available on the excretion of ifosfamide into the mother’s milk. 没有可靠证据证明异环磷酰胺可分泌到母乳中。 Ifosfamide (and its metabolites) are mainly eliminated via the kidneys. 异环磷酰胺及其代谢产物主要通过肾脏排出体外。 About 15-53% of the ifosfamide dose is excreted unchanged. 约15-35%的异环磷酰胺以原形排出体外。 异环磷酰胺的副作用（1） The dose-limiting side effects of ifosfamide are myelosuppression and urotoxicit