Core--Pharmacology- Shared Resource

自 1999 年以来，药理学核心通过提供样本处理和跟踪、药物水平分析和药代动力学建模以及研究设计和数据解释方面的协助来支持临床试验和临床前研究。在 2000-2003 年资助期间，Core 开发并向客户提供了两项新服务。一项新的分析服务是量化实体瘤中的药物分布，该服务已被发育治疗学、分子生物学和人类遗传学项目使用。基于这一经验，目前正在提供该服务来量化临床试验参与者活检中的研究药物水平。第二个新服务是人体安全药理学的体外评价 研究药物使用剂量限制组织中测量药物对正常人类靶细胞的不良影响。 Core 提供了对骨髓中正常中性粒细胞祖细胞 (CFU-GM) 的毒性的体外测定，其性能和临床预测性已在一项以 Core 为主要参与者的双盲国际研究中得到正式验证。该服务是核心活动增加的一个新兴领域，已被三个 CCC 项目用于预测营养药物化疗的人体安全性 联合治疗方案以及新颖的类似物系列正在进入临床试验 化合物。随着新服务的增加，药理学核心在样品处理、药代动力学、药物相互作用、药效学和人体安全药理学领域提供广泛、全面的药理学支持。在 2000-2003 年资助期间，发展治疗计划是药理学支持服务的主要用户，尽管所有 CCC 计划都使用该核心的一项或多项服务。核心的样本处理生成了 17,000 多个用于药理学研究的临床样本（8,000 多个来自 NIH 资助的临床试验），其中 6,000 多个 样品保留在核心中用于 HPLC 和 CFU-GM 分析。该核心预计，对药物分析和人类安全药理学服务的需求将从药物化合物转向影响化疗效果的营养保健品和膳食物质，并更加重视小分子生物标志物的测量。

Since 1999, the Pharmacology Core has supported clinical trials as well as preclinical studies by providing specimen processing and tracking, drug level analyses and pharmacokinetic modeling, and assistance in study design and data interpretation. During the 2000-2003 funding period, the Core developed and offered two new services to clients. One new analytical service is quantifying drug disposition in solid tumors, which was used by the Developmental Therapeutics and Molecular Biology & Human Genetics Programs. Based on this experience, the service is currently being offered for quantifying investigational drug levels in biopsies from clinical trial participants. The second new service is the in vitro evaluation of human safety pharmacology of investigational agents using measurements of adverse drug effects on normal human target cells from dose-limiting tissues. The Core offers an in vitro assay of toxicity to the normal neutrophil progenitor (CFU-GM) in bone marrow, the performance and clinical predictivity of which have been formally validated in a blinded, international study that included the Core as a major participant. This service is an emerging area of increased activity for the Core, having been used by three CCC programs to predict the human safety of nutraceutical-chemotherapy combination regimens being advanced to clinical trials, as well as analog series of novel compounds. With the addition of the new services, the pharmacology Core offers broad, comprehensive pharmacology support in the areas of sample handling, pharmacokinetics, drug-drug interaction, pharmacodynamics, and human safety pharmacology. During the 2000-2003 funding period, the Developmental Therapeutics Program was the major user of pharmacology support services, although all CCC programs used one or more services from this Core. Specimen processing by the Core generated over 17,000 clinical samples for pharmacology studies (over 8,000 from NIH funded clinical trials), of which over 6,000 samples remained in the Core for HPLC and CFU-GM analyses. The Core anticipates that the demand on drug analysis and human safety pharmacology services will shift from pharmaceutical compounds to nutraceuticals and dietary substances that influence the effectiveness of chemotherapy, as well as toward increased emphasis on measurements of small molecule biomarkers.