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 Nitro-20（S）丙型丙酸甲酯（9NCP）是一种有效的抗肿瘤剂，它通过摄入拓扑异构酶I的作用。研究人员预计，它将有效地针对各种癌症。 I期研究将在M.D. Anderson癌症中心进行，以找到最大的耐受剂量。 该研究在UCRC中的目的是对口服吸收后的9NCP进行药理学研究。 Camptothecin具有不稳定的内酯环（活性形式），可以在存在人白蛋白或基本pH的情况下打开以给出羧酸盐形式（非活性形式）。 凸孔塞蛋白已添加了一个支撑侧链，以保护内酯形式。 研究人员将在口服吸收后测量保持内酯形式的药物量。 为此，在药物摄入后的特定时间将抽取血液样本，为72至120小时。 样品将分析内酯和总药物含量。 将使用计算机化药理学计划来估计曲线，T Max，C Max和总体间隙下的面积。