9 NITRO 20 CAMPTOTHECIN PROPIONATE IN PTS W/ ADVANCED MALIGNANCIES

9 硝基 20 喜树碱丙酸酯治疗患有晚期恶性肿瘤的 PTS

• 批准号: 6265672
• 负责人: Claire F. Verschraegen
• 金额: $ 1.11万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265672
• 关键词: DNA topoisomerases; antineoplastics; blood chemistry; camptothecin; clearance rate; clinical research; clinical trial phase I; drug metabolism; drug screening /evaluation; enzyme inhibitors; gastrointestinal drug absorption; human subject; human therapy evaluation; lactones; metastasis; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; pharmacokinetics; propionates

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.

9硝基-20（S）喜树碱丙酸酯（9 NCP）是一种通过抑制拓扑异构酶I而发挥作用的抗肿瘤药物。研究人员预计，它将对多种癌症有效。 I期研究将在M.D.进行。安德森癌症中心寻找最大耐受剂量。 UCRC研究的目的是对口服吸收后的9 NCP进行药理学研究。 喜树碱具有不稳定的内酯环（活性形式），在人白蛋白存在下或在碱性pH下，该内酯环可以打开以产生羧酸盐形式（非活性形式）。已将丙酸酯侧链添加到喜树碱中，以保护内酯形式。 研究者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采集血液样本，持续72至120小时。 将分析样品的内酯和总药物含量。 将使用计算机药理学程序估计曲线下面积、Tmax、Cmax和全身清除率。