PHARMACOLOGIC AND PHASE I STUDIES OF NEW AGENTS FOR THE TREATMENT OF HUMAN SOLID

治疗人体固体的新药剂的药理学和一期研究

• 批准号: 6290856
• 负责人: CHRIS H. TAKIMOTO
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290856
• 关键词: alternative medicine; antineoplastics; clinical research; clinical trial phase I; drug design /synthesis /production; drug screening /evaluation; gas chromatography; human subject; human therapy evaluation; liquid chromatography; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; pyrimidines

Drug development of new anticancer agent typically involved extensive studies of drug mechanisms of action at the biochemical and molecular level. In humans, initial studies of ne molecular entities traditionally incorporate measurement of drug pharmacokinetics and pharmacodynamics into early phase I studies. However, intracellular measurement of drug effects are less common due to obvious technical and logistical difficulties in study human subjects. Furthermore, the exact reasons why promising new drugs fail to generate anticancer activity in early clinical trials are frequently unknown. Only by designing scientifically sound clinical trials that combine traditional pharmacokinetic endpoint with intracellular pharmacodynamic measurements can we hope to obtain a better understanding of the precise actions of new drugs in humans. This approach will hopefully elucidate why new treatments under study in our clinical trial do or do not work. Currently, our laboratory is applying analytic techniques such as gas and liquid chromotagraphy with mass spectroscopic detection to phase I clinical studies. These include studies of biochemical modulation of fluorinated pyrimidines, using inhibitors of pyrimidine metabolism, such as eniluracil. Other ongoing or planned agents under study include 17-allylamino-17-demethoxygeldanamycin, a novel agent that targets head shock proteins, and genistein, a natural product derived from soy beans with cancer preventative and growth inhibitory properties. Finally, because of the potential impact of the use of alternative medicines in patients enrolled in phase I studies, we are examining the prevalence and types of alternative medicine popular in our study populations. - colorectal cancer,

新抗癌剂的药物开发通常涉及在生物化学和分子水平上对药物作用机制的广泛研究。在人类中，新分子实体的初始研究传统上将药物药代动力学和药效学的测量纳入早期I期研究。然而，由于在研究人类受试者中明显的技术和后勤困难，药物作用的细胞内测量不太常见。此外，有前途的新药在早期临床试验中未能产生抗癌活性的确切原因往往是未知的。只有通过设计科学合理的临床试验，将联合收割机传统的药代动力学终点与细胞内药效学测量相结合，我们才有希望更好地了解新药在人体中的确切作用。这种方法有望阐明为什么我们的临床试验中正在研究的新治疗方法有效或无效。目前，我们的实验室正在应用分析技术，如气相色谱和液相色谱质谱检测到I期临床研究。这些研究包括使用嘧啶代谢抑制剂（如eniluracil）对氟化嘧啶进行生物化学调节的研究。其他正在进行或计划研究的药物包括17-烯丙基氨基-17-去甲氧基格尔德霉素，一种靶向头部休克蛋白的新型药物，以及染料木黄酮，一种来自大豆的天然产物，具有预防癌症和抑制生长的特性。最后，由于在I期研究中招募的患者中使用替代药物的潜在影响，我们正在检查我们研究人群中流行的替代药物的流行率和类型。- 结肠直肠癌，