Anticancer Drug Pharmacology in Very Young Children
幼儿抗癌药物药理学
基本信息
- 批准号:8658033
- 负责人:
- 金额:$ 42.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-09 至 2017-04-30
- 项目状态:已结题
- 来源:
- 关键词:1 year old3 year oldAccountingAddressAdultAffectAgeAntineoplastic AgentsAntitumor ResponseApplications GrantsBody SizeBody WeightBrain NeoplasmsCharacteristicsChildChildhoodChronicClinicalClinical PharmacologyClinical ProtocolsClinical TrialsCoupledCyclophosphamideDataDerivation procedureDevelopmentDoseDrug DesignDrug KineticsDrug usageEventExcretory functionExposure toGenetic PolymorphismGoalsHepaticHigh Dose ChemotherapyIncidenceIndividualInfantInfectionIntravenousKidneyKnowledgeLate EffectsLifeLiverMalignant NeoplasmsMalignant neoplasm of brainMedicalMetabolismMethotrexateModelingMorbidity - disease rateMyelosuppressionNeutropeniaOralOrganPatientsPharmaceutical PreparationsPharmacodynamicsPharmacogeneticsPharmacologyPhysiologicalPlasmaPopulationRecommendationRegimenResearch PersonnelRiskRisk FactorsTherapeutic IndexTissuesTopotecanToxic effectabsorptionage groupage relatedbasechemotherapydesigndosageevidence baseimprovedinfancyinfant outcomeirradiationpatient populationpharmacodynamic modelpharmacokinetic modelresponsetumor
项目摘要
DESCRIPTION (provided by applicant): Although anti-cancer drugs are widely used in infants and young children with malignant brain tumors, the dosing of these toxic drugs is often scaled based on body size (e.g., BSA or body weight) or arbitrary age cut-offs. This dosing approach does not take into account the many developmental changes that occur in infants and young children. These changes, which include hepatic and renal maturation, may affect the disposition of anticancer drugs, leading to more severe toxicity, particularly myelosuppression, which puts these children at risk of life-threatening infections. Yet the pharmacokinetics and toxicity of many anticancer drugs have not been adequately studied in infants and young children. Thus, we propose to perform clinical pharmacokinetic (PK), pharmacogenetic, and pharmacodynamic (PD) studies of methotrexate (MTX), cyclophosphamide (CTX), and topotecan (TPT) as part of a clinical protocol that treats infants and young children with malignant brain tumors. In this grant application, we propose three hypothesis directed aims: 1.) To characterize the disposition of MTX, oral and intravenous CTX, and oral and intravenous TPT in infants and young children with malignant brain tumors, 2.) To use statistical and mechanistic models to identify PD and PKPD response relationships for anti-cancer drugs in infants and young children, and 3.) To develop dosing regimens for infants and young children to achieve more uniform systemic exposure to anticancer drugs across all pediatric age groups. Collectively, these studies narrow the gap in our understanding of the clinical pharmacology of anti-cancer drugs used to treat infants and young children. Our long-term goal is to determine rational dosing regimens for infants and young children by better understanding the developmental pharmacology of anti-cancer drugs and to apply these regimens to therapy for other childhood malignancies and chronic medical conditions.
描述(由申请人提供):尽管抗癌药物广泛用于患有恶性脑肿瘤的婴儿和幼儿,但这些毒性药物的剂量通常基于体型(例如,BSA或体重)或任意年龄临界值。这种给药方法没有考虑到婴儿和幼儿发生的许多发育变化。这些变化,包括肝脏和肾脏的成熟,可能会影响抗癌药物的处置,导致更严重的毒性,特别是骨髓抑制,使这些儿童面临危及生命的感染风险。然而,许多抗癌药物的药代动力学和毒性尚未在婴儿和幼儿中得到充分研究。因此,我们建议对甲氨蝶呤(MTX)、环磷酰胺(CTX)和拓扑替康(TPT)进行临床药代动力学(PK)、药物遗传学和药效学(PD)研究,作为治疗患有恶性脑肿瘤的婴幼儿的临床方案的一部分。在本申请中,我们提出了三个假设指导目标:1。描述MTX、口服和静脉注射CTX以及口服和静脉注射TPT在患有恶性脑肿瘤的婴幼儿中的分布,2.)使用统计学和机制模型来确定PD和PKPD对婴幼儿抗癌药物的反应关系,以及3.)为婴幼儿制定给药方案,以使所有儿科年龄组的抗癌药物全身暴露更加均匀。总的来说,这些研究缩小了我们对用于治疗婴儿和幼儿的抗癌药物临床药理学理解的差距。我们的长期目标是通过更好地了解抗癌药物的发育药理学来确定婴幼儿的合理给药方案,并将这些方案应用于其他儿童恶性肿瘤和慢性疾病的治疗。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
CLINTON F STEWART其他文献
CLINTON F STEWART的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('CLINTON F STEWART', 18)}}的其他基金
Anticancer Drug Pharmacology in Very Young Children
幼儿抗癌药物药理学
- 批准号:
8295086 - 财政年份:2012
- 资助金额:
$ 42.05万 - 项目类别:
Anticancer Drug Pharmacology in Very Young Children
幼儿抗癌药物药理学
- 批准号:
8841683 - 财政年份:2012
- 资助金额:
$ 42.05万 - 项目类别:
Anticancer Drug Pharmacology in Very Young Children
幼儿抗癌药物药理学
- 批准号:
8507616 - 财政年份:2012
- 资助金额:
$ 42.05万 - 项目类别:
TRIALS OF CLADRIBINE PLUS OTHER AGENTS FOR PEDIATRIC AML
克拉屈滨联合其他药物治疗儿童 AML 的试验
- 批准号:
6173819 - 财政年份:1999
- 资助金额:
$ 42.05万 - 项目类别:
相似海外基金
Development and social implementation of unified developmental screening for health checkups for 3-year-old children in local governments
地方政府统一开展3岁儿童健康检查发育筛查工作的开展及社会实施
- 批准号:
23H01039 - 财政年份:2023
- 资助金额:
$ 42.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Low vision screening at 3-year-old children's health check-ups: development of a simple and accurate visual acuity testing software
3岁儿童体检中的低视力筛查:开发简单准确的视力测试软件
- 批准号:
23K02283 - 财政年份:2023
- 资助金额:
$ 42.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
0-3-year-old children's language and literacy learning at home in a digital age (0-3s, Tech and Talk)
数字时代0-3岁儿童在家学习语言和识字(0-3s,Tech and Talk)
- 批准号:
ES/W001020/1 - 财政年份:2022
- 资助金额:
$ 42.05万 - 项目类别:
Research Grant
Associations between physical activity levels of mothers and their 1-3 year old children: examining maternal self-efficacy as a mediator
母亲和 1-3 岁孩子体力活动水平之间的关联:检查作为中介的母亲自我效能感
- 批准号:
324339 - 财政年份:2015
- 资助金额:
$ 42.05万 - 项目类别:
Lived time of 3-year-old children in early childhood education and care: Reconsidering continuity of life and development
3岁儿童在幼儿教育和保育中的生存时间:重新思考生命和发展的连续性
- 批准号:
15K17356 - 财政年份:2015
- 资助金额:
$ 42.05万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Development of family support program to form healthy 3-year-old children and their mothers
制定家庭支持计划,培养健康的3岁儿童及其母亲
- 批准号:
24593457 - 财政年份:2012
- 资助金额:
$ 42.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
SUPPORTING 2 AND 3 YEAR OLD PRE-KINDERGARTEN READINESS
支持 2 岁和 3 岁儿童做好学前准备
- 批准号:
7699693 - 财政年份:2008
- 资助金额:
$ 42.05万 - 项目类别:
ADENOIDECTOMY FOR OTITIS MEDIA IN 2/3 YEAR OLD CHILDREN
2/3 岁儿童中耳炎的腺切除术
- 批准号:
6350559 - 财政年份:1997
- 资助金额:
$ 42.05万 - 项目类别:
EMOTIONAL AND BEHAVIOR PROBLEMS IN 1-3 YEAR OLD CHILDREN
1-3 岁儿童的情绪和行为问题
- 批准号:
2890762 - 财政年份:1997
- 资助金额:
$ 42.05万 - 项目类别:
EMOTIONAL AND BEHAVIOR PROBLEMS IN 1-3 YEAR OLD CHILDREN
1-3 岁儿童的情绪和行为问题
- 批准号:
2841735 - 财政年份:1997
- 资助金额:
$ 42.05万 - 项目类别: