9 NITRO 20 CAMPTOTHECIN PROPIONATE IN PTS W/ ADVANCED MALIGNANCIES

9-硝基-20(S)丙酸喜树碱(9NCP)是一种通过诱导拓扑异构酶I发挥作用的有效抗肿瘤药物。研究人员预计，它将对多种癌症有效。一期研究将在M.D.安德森癌症中心进行，以确定最大耐受量。UCRC的这项研究的目的是对口服吸收的9NCP进行药理学研究。喜树碱有一个不稳定的内酯环(活性形式)，在人血清白蛋白存在下或在碱性pH下，它可以被打开而得到羧酸盐形式(非活性形式)。在喜树碱中添加了一条专有的侧链，以保护内酯不受影响。研究人员将测量口服吸收后仍以内酯形式存在的药物的量。为此，将在服药后的特定时间抽取血液样本，时间为72至120小时。样品将被分析内酯和总药物含量。计算机药理学程序将被用来估计曲线下的面积、Tmax、Cmax和全身清除量。

9 Nitro-20(S) camptothecin propionate (9NCP) is a potent antitumor agent which works through ingibition of topoisomerase I. The investigators anticipate that it will be effective against a variety of cancers. A Phase I study will be conducted at M.D. Anderson Cancer Center to find the maximum tolerated dose. The aim of the study at the UCRC is to perform a pharmacology study of 9NCP after oral absorption. Camptothecin has a labile lactone ring (active form) which can be opened to give a carboxylate form (inactive form) in the presence of human albumin, or at basic pH. A proprionate side chain has been added to the camptothecin, to protect the lactone form. The investigators will measure the amount of drug that remains in lactone form after oral absorption. For this, samples of blood will be drawn at specific times after drug intake, for a period of 72 to 120 hours. Samples will be analyzed for the lactone and total drug content. A computerized pharmacology program will be utilized to estimate the area under the curve, T max, C max, and total body clearance.