9 NITRO 20 CAMPTOTHECIN PROPIONATE IN PTS W/ ADVANCED MALIGNANCIES

硝基-20(S)喜树碱丙酸酯（9NCP）是一种有效的抗肿瘤药物，通过激活拓扑异构酶i起作用。研究人员预计它将对多种癌症有效。一项I期研究将在安德森癌症中心进行，以找到最大耐受剂量。UCRC研究的目的是对口服吸收后的9NCP进行药理学研究。喜树碱具有一个不稳定的内酯环（活性形式），在人白蛋白存在下或在碱性ph下可打开形成羧酸盐形式（无活性形式）。喜树碱中添加了一个本体侧链，以保护内酯形式。研究人员将测量口服吸收后仍以内酯形式存在的药物量。为此，将在药物摄入后的特定时间抽取血液样本，持续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用于估计曲线下面积，tmax， cmax和全身清除率。

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.