药代动力学
体内分布
药理学
治疗指标
脂质体
分布(数学)
喜树碱
化学
拓扑替康
药品
分配量
医学
化疗
内科学
体外
生物化学
数学分析
数学
作者
David L. Emerson,Raymond A. Bendele,Eric N. Brown,SuMing Chiang,John Desjardins,Larry Dihel,Stan Gill,Marta Hamilton,J Leray,Lotus Moon-McDermott,Karen Moynihan,Frank C. Richardson,Blake Tomkinson,Michael J. Luzzio,David P. Baccanari
出处
期刊:PubMed
日期:2000-07-01
卷期号:6 (7): 2903-12
被引量:16
摘要
Lurtotecan is a clinically active water-soluble camptothecin analogue that has been formulated into a low-clearance unilamellar liposome, NX 211. Comparative studies between free drug and NX 211 have been performed assessing pharmacokinetics in nude mice, tissue distribution in tumor-bearing mice, and antitumor efficacy in xenografts. Compared with lurtotecan, NX 211 demonstrated a significant increase in plasma residence time and a subsequent 1500-fold increase in the plasma area under the drug concentration curve. The volume of distribution was also greatly restricted, suggesting altered tissue distribution. Evaluation of tissues 24 h after administration of either [14C]NX 211 or [14C]lurtotecan to ES-2 tumor-bearing mice demonstrated a 40-fold increase in radiolabeled compound in the tumors of NX 211-treated mice compared with mice treated with lurtotecan. In single-dose efficacy studies, NX 211 produced a consistent 3-fold or greater increase in therapeutic index compared with lurtotecan in both the KB and ES-2 xenograft models. When compared at equitoxic levels in repeat-dose efficacy studies, NX 211 generated durable cures lasting >60 days and a 2-8-fold increase in log10 cell kill, compared with lurtotecan and topotecan, respectively. Together, these data demonstrate that NX 211 has significant therapeutic advantage over lurtotecan and that the improved antitumor activity is consistent with increased exposure and enhanced drug delivery to tumor sites.
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