A PHARMACOKINETIC AND PHARMACOGENETIC STUDY OF CHEMOTHERAPEUTIC

化疗药物的药代动力学和药物遗传学研究

• 批准号: 7606415
• 负责人: CHRISTOPHER J SWEENEY
• 金额: $ 1.23万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606415
• 关键词: Anthracycline Antibiotics; Anthracyclines; Class; Clinical; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450 3A4; Dose; Drug Kinetics; Enzymes; Exposure to; Funding; Germ cell tumor; Glycoproteins; Grant; Institution; Lymphoma; Malignant Neoplasms; Outcome; Patients; Pharmaceutical Preparations; Pharmacogenetics; Research; Research Personnel; Resources; Solid; Source; Taxane Compound; Therapeutic; Toxic effect; United States National Institutes of Health; Vinca Alkaloids; experience; taxane

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The vinca alkaloids, anthracyclines, taxanes and podophylotoxins are important classes of chemotherapeutic drugs in both hematological and solid malignancies. Despite this, there is relatively little information available regarding the disposition and optimal dosing of these agents. Prior pharmacokinetic studies have documented substantial inter-patient variability and clinical use is associated with unpredictable toxicities. It is desirable to optimize the dosing of these classes of agents especially as they are all used to treat curable malignancies including lymphomas and germ cell tumors. A pharmacogenetic study of enzymes that metabolize (cytochrome P450 3A4) and/or transport (p-glycoprotein) these agents paired with a pharmacokinetic analysis will provide a better understanding of the disposition of these agents. This increased understanding will help us better predict who gains an excess exposure to the drug and hence experience increased toxicity as well as those with potentially sub-therapeutic drug levels and potentially a poorer outcome from under-dosing.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 VINCA生物碱，蒽环类动物，紫杉烷和podophyloxoins是血液学和固体恶性肿瘤中的化学治疗药物的重要类别。 尽管如此，有关这些药物的处置和最佳剂量的可用信息相对较少。 先前的药代动力学研究已证明了大量的患者间变异性，临床使用与不可预测的毒性有关。 希望优化这些类别的药物的剂量，尤其是因为它们都用于治疗包括淋巴瘤和生殖细胞肿瘤在内的可治愈的恶性肿瘤。 这些代谢（细胞色素P450 3A4）和/或转运（P-糖蛋白）的药物遗传学研究这些及其与药代动力学分析配对的药物将更好地理解这些药物的处置。 这种增强的理解将有助于我们更好地预测谁获得了对药物的过量暴露，因此经历增加了毒性以及潜在的亚治疗水平的人，并且剂量不足的结果可能较差。