Antitumor effects of CPT-11 liposomes on HT-29 Xenograft and PK/PD correlation evaluation

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	Antitumor effects of CPT-11 liposomes on HT-29 Xenograft and PK/PD correlation evaluation
	Li Ning 2; Zhang Qing1 ; Jia Linchao 3; Zheng Qingmei 3; Yan Lei 1; Liu Jingli 1; Yu Qiang1 ; Gong Xinjiang 3
刊名	Chinese Journal New Drugs
	2014
卷号	23 期号:6 页码:721-726
关键词	CPT-11 CPT-11 liposome antitumor PK/PD correlation
ISSN号	1003-3734
其他题名	CPT-11脂质体对人结肠癌HT-29移植瘤的抗肿瘤活性及药代-药效相关性分析
文献子类	Article
英文摘要	Objective: To investigate inhibitory effects of CPT-11 liposome (lipoCPT-11) on human colon HT-29 xenografts in nude mice, and measure concentrations of parent drug CPT-11 and it's active metabolite SN-38 in plasma and tumor tissue, so as to evaluate the PK/PD correlation of lipoCPT-11. Methods: HT-29 colon cells were inoculated subcutaneously to nude mice to establish xenografts model. In efficacy study, lipoCPT-11 was administered at doses of 5, 25 and 50mg·kg~(-1) while commercial common formulation of irinotecan (cCPT-11) was dosed at 50mg·kg~(-1), with the same schedule of iv, twice weekly for three weeks. In PK/PD research, lipoCPT-11 was intravenously injected at 50 and 50mg·kg~(-1), compared with cCPT-11 of 50mg·kg~(-1), and tumor tissue and plasma were collected at designed timepoints, thereafter CPT-11 and SN-38 concentrations were measured respectively by the validated LC-MS/MS methods. Results: lipoCPT-11 could distinctly inhibit growth of HT-29 xenografts with a significant dose-dependent manner at dose of 5, 25 and 50mg·kg~(-1). At the equivalent dose of 50mg·kg~(-1), lipoCPT-11 was of higher potency than that of cCPT-11. After lipoCPT-11 was administrated, the retention time of CPT-11 and SN-38 in tumor and plasma were longer than cCPT-11, with increased AUC_(0-t) of 426.1 and 5.0-fold in plasma and 9.5 and 5.0 fold in tumor, and interestingly, at the 1/10 dose of 50mg·kg~(-1) cCPT-11, lipoCPT-11 possessed 31.1 and 0.4-fold exposure of CPT-11 in plasma and tumor, and in the case of SN-38, the ratios were both 1.0-fold. Conclusion: lipoCPT-11 could strongly increase antitumor activity of cCPT-11, which was well elucidated by its long retention time and improved effective exposure in plasma and tumor, therefore exhibited pivotal clinical application value and promising development prospects.
资助项目	国家"重大新药创制"科技重大专项[00000000] ; 济南大学博士基金[00000000]
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:5105403
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/269341]
专题	药理学第一研究室
作者单位	1.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.; 2.School of Medicine and Life Sciences, University of Jinan, Jinan, Shandong 250022, China.; 3.Qilu Pharmaceutical Research Institute, Qilu Pharmaceutical Co., Ltd., Jinan, Shandong 250100, China.
推荐引用方式 GB/T 7714	Li Ning,Zhang Qing,Jia Linchao,et al. Antitumor effects of CPT-11 liposomes on HT-29 Xenograft and PK/PD correlation evaluation[J]. Chinese Journal New Drugs,2014,23(6):721-726.
APA	Li Ning.,Zhang Qing.,Jia Linchao.,Zheng Qingmei.,Yan Lei.,...&Gong Xinjiang.(2014).Antitumor effects of CPT-11 liposomes on HT-29 Xenograft and PK/PD correlation evaluation.Chinese Journal New Drugs,23(6),721-726.
MLA	Li Ning,et al."Antitumor effects of CPT-11 liposomes on HT-29 Xenograft and PK/PD correlation evaluation".Chinese Journal New Drugs 23.6(2014):721-726.