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

新型抗癌剂的药物开发 通常涉及对药物作用机制的广泛研究 生化和分子水平。在人类中，对NE的初步研究 分子实体传统上包括药物的测量 药代动力学和药效学进入早期I期研究。 然而，药物效应的细胞内测量较少。 由于学习中明显的技术和后勤困难而常见 人类受试者。此外，有希望的新技术之所以 在早期临床试验中未能产生抗癌活性的药物是 通常不为人所知。只有通过设计科学合理的临床 将传统药代动力学终点与 细胞内药效学测量我们可以期待 更好地了解新药在中国的确切作用 人类。这种方法有望阐明为什么新的治疗方法 在我们的临床试验中正在研究是否有效。目前，我们的 实验室正在应用气体和液体等分析技术 I相的色谱联用质谱仪检测 临床研究。这些包括对生物化学调节的研究 使用嘧啶代谢抑制剂的氟化嘧啶类化合物， 如苯氧尿嘧啶。其他正在进行或计划中的研究中的药物 包括新型药物17-烯丙氨基-17-去甲氧基格尔达那霉素 它针对的是头部休克蛋白和天然产物染料木素 从具有防癌和生长作用的大豆中提取 抑制特性。最后，由于 在第一阶段研究中登记的患者使用替代药物， 我们正在研究替代医学的流行率和类型 在我们的研究人群中很受欢迎。

"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 agents 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."