Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters.
Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters.
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DOI：
10.1038/sj.bjc.6690450
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发表时间：
1999-06
影响因子：
8.8
通讯作者：
Bartus, RT
中科院分区：
文献类型：
--
作者：
Emerich, DF;Snodgrass, P;Dean, R;Agostino, M;Hasler, B;Pink, M;Xiong, H;Kim, BS;Bartus, RT
CereportTM（RMP-7）是一种选择性缓激肽B2受体激动剂，可增加“血脑肿瘤屏障”（BBTB）的通透性，从而增加化疗药物向脑肿瘤的输送。在神经胶质瘤的RG 2啮齿动物模型中进行一系列实验以评估和改进静脉内（i. v.）优化Cereport的临床效用。第一个实验表明，虽然在Cereport输注期间作为推注给予时卡铂水平增加了两倍，但当Cereport和卡铂同时共输注15分钟时，未观察到卡铂水平增加。随后的实验确定，造成共输注范例缺乏效果的主要因素是在15分钟输注期间对Cereport的快速耐受，在此期间，随着卡铂血浆水平的升高，对Cereport的反应逐渐减弱。最终实验调整了Cereport和卡铂输注的时间，以便在开始Cereport输注之前达到更高的血浆卡铂水平。当卡铂输注先于Cereport输注10 min（即两种药物的输注重叠5 min）时，获得了显著的摄取效应。总的来说，这些数据提供了涉及受体介导的BBTB渗透性变化的给药参数的首次系统评价，并提供了有关Cereport药效学和潜在临床用途的新信息。© 1999癌症研究运动
CereportTM (RMP-7) is a selective bradykinin B2 receptor agonist which increases the permeability of the ‘blood–brain tumour barrier’ (BBTB) to increase delivery of chemotherapeutic agents to brain tumours. A series of experiments was performed in an RG2 rodent model of glioma to evaluate and refine intravenous (i.v.) parameters to optimize Cereport's clinical utility. The first experiment demonstrated that while carboplatin levels were increased by twofold when given as a bolus during the Cereport infusion, no increase in carboplatin levels were seen when Cereport and carboplatin were simultaneously co-infused for 15 min. A subsequent experiment established that a major factor responsible for the lack of an effect with the co-infusion paradigm was tachyphylaxis to Cereport during the 15 min infusion, for a progressively diminished response to Cereport occurred over that time frame, as plasma levels of carboplatin were rising. A final experiment adjusted the timing of the Cereport and carboplatin infusions so that higher plasma carboplatin levels were achieved prior to initiating the Cereport infusion. Significant uptake effects were achieved when the carboplatin infusion preceded the Cereport infusion by 10 min (i.e. 5 min overlap in the delivery of the two agents). Collectively, these data provide the first systematic evaluation of dosing parameters involving receptor-mediated changes in BBTB permeability and provide new information regarding the pharmacodynamics and potential clinical use of Cereport. © 1999 Cancer Research Campaign
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