Pharmacogenetic Determinants of Vinca Alkaloid Response
长春花生物碱反应的药物遗传学决定因素
基本信息
- 批准号:6927525
- 负责人:
- 金额:$ 13.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-09-01 至 2010-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant):
The investigator's long-term career objective is to become an independent clinician-scientist and educator in the fields of pediatric pharmacology, pharmacogenetics and pediatric hematology/oncology. This application involves formal didactic training in clinical research skills and a focused research proposal designed to form the foundation for a career in clinical research. Through participation in the Indiana University K30 program, the applicant will receive the didactic training necessary for a research career in clinical pharmacology. The candidate has the full support of the Chairman of Pediatrics and the Director of the GCRC and will perform her research in an outstanding clinical research environment. The proposed projects aim to determine which enzymes are involved in vinca alkaloid disposition and whether genetic polymorphisms in these enzymes and the membrane transporters that carry the vinca alkaloids are predictive of disposition, efficacy and toxicity. Despite the long history of vinca alkaloid use in oncology, the precise roles of the cytochrome P450 enzymes in their disposition remain largely uncharacterized. This is important because there is no definitive explanation for the significant variability in the pharmacokinetics of these drugs. As a result, pharmacokinetic or pharmacogenetic parameters that might predict vinca alkaloid toxicity and outcome have not been identified. The first aim of this proposal involves identification of the major metabolites of the vinca alkaloids, the enzymes involved in their production, and quantification of Michaelis Menten kinetic parameters for these enzymes. The second aim investigates the impact of pharmacogenetic polymorphisms in pertinent drug metabolizing enzymes and transporters on vinca alkaloid pharmacokinetics, toxicity, and efficacy in pediatric and adult cancer patients. Through these projects, this investigator will work toward her long-range research goal of understanding how genetic polymorphisms in drug metabolizing enzymes, receptors, and transporters influence the efficacy and toxicity of drugs in pediatric and adult cancer patients.
描述(由申请人提供):
研究人员的长期职业目标是成为儿科药理学、药物遗传学和儿科血液学/肿瘤学领域的独立临床科学家和教育者。这项申请涉及临床研究技能的正式教学培训和旨在形成临床研究职业生涯基础的重点研究方案。通过参加印第安纳大学K30项目,申请者将接受临床药理学研究生涯所需的教学培训。候选人得到了儿科主席和GCRC主任的全力支持,并将在出色的临床研究环境中进行研究。拟议的项目旨在确定哪些酶参与长春花碱的处置,以及这些酶和携带长春花碱的膜转运蛋白的遗传多态是否可以预测处置、疗效和毒性。尽管长春花碱在肿瘤学中的使用有很长的历史,但细胞色素P450酶在其处置中的确切作用在很大程度上仍不清楚。这一点很重要,因为对这些药物的药代动力学的显著差异没有明确的解释。因此,可能预测长春花碱毒性和结局的药代动力学或药物遗传学参数尚未确定。这项建议的第一个目标是确定长春花碱的主要代谢物、参与其生产的酶,并量化这些酶的Michaelis Menten动力学参数。第二个目的是研究相关药物代谢酶和转运蛋白的药物遗传多态性对长春花碱在儿童和成人癌症患者中的药代动力学、毒性和疗效的影响。通过这些项目,这位研究人员将朝着她的长期研究目标努力,即了解药物代谢酶、受体和转运体的基因多态性如何影响儿童和成人癌症患者的药物疗效和毒性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JAMIE L RENBARGER其他文献
JAMIE L RENBARGER的其他文献
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{{ truncateString('JAMIE L RENBARGER', 18)}}的其他基金
Indiana University Center for Pediatric Pharmacology and Precision Medicine
印第安纳大学儿科药理学和精准医学中心
- 批准号:
9974297 - 财政年份:2016
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vincristine Toxicity and Response
长春新碱毒性和反应的药物遗传学决定因素
- 批准号:
8016176 - 财政年份:2011
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vincristine Toxicity and Response
长春新碱毒性和反应的药物遗传学决定因素
- 批准号:
8431768 - 财政年份:2011
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vincristine Toxicity and Response
长春新碱毒性和反应的药物遗传学决定因素
- 批准号:
8206474 - 财政年份:2011
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vincristine Toxicity and Response
长春新碱毒性和反应的药物遗传学决定因素
- 批准号:
8601739 - 财政年份:2011
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vincristine Toxicity and Response
长春新碱毒性和反应的药物遗传学决定因素
- 批准号:
8777099 - 财政年份:2011
- 资助金额:
$ 13.63万 - 项目类别:
Developing a prediction model for vincristine-induced peripheral neuropathy
开发长春新碱引起的周围神经病变的预测模型
- 批准号:
7943956 - 财政年份:2009
- 资助金额:
$ 13.63万 - 项目类别:
Developing a prediction model for vincristine-induced peripheral neuropathy
开发长春新碱引起的周围神经病变的预测模型
- 批准号:
7832766 - 财政年份:2009
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vinca Alkaloid Response
长春花生物碱反应的药物遗传学决定因素
- 批准号:
7640749 - 财政年份:2005
- 资助金额:
$ 13.63万 - 项目类别:
Pharmacogenetic Determinants of Vinca Alkaloid Response
长春花生物碱反应的药物遗传学决定因素
- 批准号:
7256373 - 财政年份:2005
- 资助金额:
$ 13.63万 - 项目类别:
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