VP16与VM26在小鼠Lewis肺癌中的比较。

Comparison between VP 16 and VM 26 in Lewis lung carcinoma of the mouse.

作者信息

Colombo T, Broggini M, Vaghi M, Amato G, Erba E, D'Incalci M

出版信息

Eur J Cancer Clin Oncol. 1986 Feb;22(2):173-9. doi: 10.1016/0277-5379(86)90027-1.

Abstract

The antitumoral activity and pharmacokinetics of VP 16 and VM 26 were comparatively investigated in Lewis lung carcinoma (3LL)-bearing mice. When the two drugs were given at equitoxic doses, in single or repeated treatment, the superior antitumoral activity of VM 26 was clear. Compared to VP 16, VM 26 had a different pattern of distribution, with a larger volume of distribution, a longer elimination half-life time and a lower clearance. The tissue to plasma AUC ratios indicated that VM 26 concentrated more in tumor and heart while VP 16 gave highest concentrations in liver and intestine. Flow cytometry studies showed that VM 26 was more potent than VP 16 in causing cell cycle perturbation of 3LL cells growing in primary culture. VM 26 displayed cytotoxic activity at a concentration in the medium one-tenth that of VP 16. The uptake of VM 26 by 3LL cells was 15 times that of VP 16.

摘要

在携带Lewis肺癌（3LL）的小鼠中对依托泊苷（VP 16）和替尼泊苷（VM 26）的抗肿瘤活性和药代动力学进行了比较研究。当以等毒性剂量给予这两种药物时，无论是单次给药还是重复给药，VM 26的抗肿瘤活性更优是显而易见的。与VP 16相比，VM 26具有不同的分布模式，分布容积更大、消除半衰期更长且清除率更低。组织与血浆的曲线下面积（AUC）比值表明，VM 26在肿瘤和心脏中浓度更高，而VP 16在肝脏和肠道中浓度最高。流式细胞术研究表明，在引起原代培养中生长的3LL细胞的细胞周期紊乱方面，VM 26比VP 16更有效。VM 26在培养基中的浓度为VP 16的十分之一时就表现出细胞毒性活性。3LL细胞对VM 26的摄取是对VP 16摄取的15倍。