CLINICAL PHARMACOLOGY

临床药理学

• 批准号: 3838115
• 负责人: D G POPLACK
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 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/3838115
• 关键词: 6 thioguanine; AIDS therapy; Primates; antiAIDS agent; antileukemic agent; antineoplastics; antiviral agents; asparaginase; carboxypeptidase; central nervous system neoplasms; child (0-11); clinical trials; cytosine analog; disease /disorder model; drug adverse effect; drug delivery systems; drug screening /evaluation; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neurotoxins; nutrition related tag; paclitaxel; pediatric AIDS; pediatric neoplasm /cancer; pediatric pharmacology; pharmacokinetics; retinoate; thiotepa

The clinical pharmacology of antineoplastic agents used in the treatment of pediatric malignancies is studied with emphasis on the role of pharmacologic monitoring and on both pre-clinical and clinical pharmacologic studies of Phase I agents. Preclinical, Phase I and pharmacokinetic studies of a variety of new agents including All-trans retinoic acid, Topotecan, Pyrazoloacridine, Taxotere, Taxol, Piroxantrone, Cyclopentenylcytosine (CPE-C) and Amifostine are in progress. In addition, Phase I, Phase II and correlative pharmacologic studies evaluating new approaches or new formulations of older chemotherapeutic agents including thiotepa, intravenous 6-thioguanine and PEG-L-asparaginase are being pursued. Phase II studies of agents previously studied both preclinically and in Phase I trials in this section are also in progress (e.g.Fazarabine, ICRF-187). Several collaborative studies in which this section provides pharmacologic support for important clinical studies in other COP Branches are being pursued. A major effort of this project is to investigate experimental approaches to the treatment of CNS malignancy. A unique primate model is utilized to study the CNS pharmacokinetics of various intrathecally and intravenously administered chemotherapeutic agents; to evaluate the neurotoxicities of various CNS treatments; and to evaluate and screen newer CNS treatment modalities and drug schedules. Information gained from the studies with this model is then applied to the design of clinical treatment protocols. Clinical studies of intrathecal AZQ, intrathecal 6-MP, and intrathecal mafosfamide, all novel approaches developed in this model, are in progress. A clinical study evaluating continuous intra-CSF drug infusion via a unique indwelling drug delivery device also is under way. Two new trials evaluating the role of systemically and intrathecally administered Carboxypeptidase-G2 have begun. As part of the Pediatric Branch AIDS research effort, the PETS Section is studying the clinical pharmacology of antiretroviral agents in children. This effort is a natural extension of our work on the clinical pharmacology of anticancer drugs, since most of the antiretroviral agents are nucleoside analogs, similar to the antimetabolites used in the treatment of pediatric cancers. The CNS pharmacology of antiretroviral therapies is being systematically evaluated in our non-human primate model, to determine which agents may be most effective against CNS HIV infection. We also participate in the design of clinical trials of antiretroviral agents in children and perform detailed pharmacokinetic studies in the patients treated on these trials.

治疗中使用的抗肿瘤药物的临床药理学 研究儿童恶性肿瘤的作用，重点是 药理学监测以及临床前和临床 I 期药物的药理学研究。 临床前、I 期和 包括全反式在内的多种新药的药代动力学研究 视黄酸、拓扑替康、吡唑吖啶、泰索帝、紫杉醇、 吡罗蒽醌、环戊烯基胞嘧啶 (CPE-C) 和氨磷汀 进步。 此外，I期、II期及相关药理 评估旧方法或新配方的研究 化疗药物包括塞替派、静脉注射 6-硫鸟嘌呤和 PEG-L-天冬酰胺酶正在研发中。 药物的 II 期研究 之前在该领域的临床前和第一阶段试验中进行过研究 部分也在进行中（例如 Fazarabine、ICRF-187）。 一些 本节提供药理学的合作研究 正在为其他 COP 分支机构的重要临床研究提供支持 追击。 该项目的一个主要工作是研究实验 中枢神经系统恶性肿瘤的治疗方法。 一个独特的灵长类动物模型是 用于研究各种鞘内注射和注射的中枢神经系统药代动力学 静脉注射化疗剂；来评估 各种中枢神经系统治疗的神经毒性；并进行评估和筛选 更新的中枢神经系统治疗方式和药物时间表。 获得的信息 然后将该模型的研究应用于设计 临床治疗方案。 鞘内注射 AZQ 的临床研究， 鞘内注射 6-MP 和鞘内注射 mafosfamide，所有新方法 该模型的开发正在进行中。 一项临床研究评估 通过独特的留置药物输送连续脑脊液内药物输注 装置也正在进行中。 两项新试验评估了 全身和鞘内施用羧肽酶-G2 开始了。 作为儿科艾滋病研究工作的一部分，PETS 该部分正在研究抗逆转录病毒药物的临床药理学 孩子们。 这项工作是我们临床工作的自然延伸 抗癌药物的药理学，因为大多数抗逆转录病毒药物 是核苷类似物，类似于中使用的抗代谢物 治疗小儿癌症。 抗逆转录病毒药物的中枢神经系统药理学 正在我们的非人类灵长类动物身上系统地评估疗法 模型，以确定哪些药物可能对 CNS HIV 最有效 感染。 我们还参与临床试验的设计 儿童抗逆转录病毒药物并进行详细的药代动力学 对这些试验中接受治疗的患者进行的研究。