Core--Pharmacology- Shared Resource

自1999年以来，药理学核心通过提供标本处理和跟踪、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，支持临床试验和临床前研究。在2000-2003年供资期间，核心方案开发并向客户提供了两项新的服务。一项新的分析服务是量化实体瘤中的药物分布，这是由发育治疗学和分子生物学与人类遗传学计划使用的。基于这一经验，目前正在提供定量临床试验参与者活检中研究药物水平的服务。第二项新服务是体外评估人体安全药理学， 使用对来自剂量限制性组织的正常人靶细胞的药物不良作用的测量来评估研究药物。Core提供了一种对骨髓中正常中性粒细胞祖细胞（CFU-GM）毒性的体外试验，其性能和临床预测性已在一项设盲的国际研究中得到正式验证，该研究包括Core作为主要参与者。这项服务是核心活动增加的一个新兴领域，已经被三个CCC项目用于预测营养药物-化疗的人类安全性 联合方案正在进入临床试验，以及一系列新的类似方案 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，药效学和人类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，发展治疗学项目是药理学支持服务的主要用户，尽管所有CCC项目都使用该核心的一项或多项服务。Core的样本处理产生了17，000多份临床样本用于药理学研究（8，000多份来自NIH资助的临床试验），其中6，000多份来自 样品保留在核心中用于HPLC和CFU-GM分析。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移到影响化疗有效性的营养保健品和膳食物质，以及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.