药物动力学和biodistribution camptothecin-polymer共轭它在大鼠和小鼠肿瘤- 101。

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程Schluep T, J,钦KT,戴维斯我

药物动力学和biodistribution camptothecin-polymer共轭它在大鼠和小鼠肿瘤- 101。

57癌症Chemother杂志。2006;(5):654 - 62。Epub 2005年8月26日。

PubMed ID

16133526 (在PubMed

]

文摘

目的:- 101是一个camptothecin-polymer共轭由连接喜树碱(CPT)亲水,cyclodextrin-based,线性聚合物通过酯键。在先前的研究中,这些使共轭聚合物与高分子量(ca 90 kDa)显示显著的抗肿瘤作用对人类结肠癌癌异种移植。它在等离子体- 101的药物动力学裸小鼠移植瘤模型大鼠及其biodistribution人类LS174T结肠癌癌肿瘤报告在这里。方法:Sprague-Dawley老鼠和三种不同剂量的静脉注射- 101。串行血浆样品分析polymer-bound和非结合的CPT的高效液相色谱法(HPLC)。浓度和时间数据建模相比,使用non-compartmentalized方法和CPT独自在同等剂量静脉注射。肿瘤小鼠静脉注射与CPT - 101和腹腔内,牺牲了24和48 h后,血清、心脏、肝、脾、肺和肿瘤的收集。组织样本进行了提取和分析polymer-bound和非结合的CPT通过高效液相色谱法。结果:血浆浓度曲线下的面积,polymer-bound CPT大约100倍高于非结合的CPT或CPT,仅在同等剂量静脉注射。血浆半衰期为17 - 101范围从-20 h和明显比CPT(1.3小时)。当CPT共轭聚合物,CPT的biodistribution模式不同于单独拍摄。 At 24 h post injection, the total CPT per gram of tissue is the highest in tumor tissue when compared to all other tissues tested. Tumor concentrations of active CPT released from the conjugate are more than 160-fold higher when administered as a polymer conjugate rather than as CPT alone. CONCLUSIONS: The studies presented here indicate that intravenous administration of IT-101, a cyclodextrin based polymer-CPT conjugate, gives prolonged plasma half-life and enhanced distribution to tumor tissue when compared to CPT alone. The data also show that active CPT is released from the conjugate within the tumor for an extended period of time. These effects likely play a significant role in the enhanced antitumor activity of IT-101 when compared to CPT alone or irinotecan.

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药物

CRLX101