ABTR06C1 PHARMACOKINETICS OF DAUNOMYCIN IN CHILDREN

ABTR06C1 道诺霉素在儿童中的药代动力学

• 批准号: 8166697
• 负责人: STACEY L BERG
• 金额: $ 0.27万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166697
• 关键词: 21 year old; Accounting; Acute Lymphocytic Leukemia; Adult; Adverse effects; Age; Anthracyclines; Antineoplastic Agents; Behavior; Blood; Body Composition; Body Size; Body Surface Area; Body Weight; Body fat; Body mass index; Child; Childhood; Computer Retrieval of Information on Scientific Projects Database; Data; Daunorubicin; Dose; Drug Kinetics; Funding; Gender; Grant; Hepatic; Institution; Kidney; Laboratories; Malignant Neoplasms; Methods; Obesity; Overweight; Patients; Pharmaceutical Preparations; Regimen; Renal function; Research; Research Personnel; Resources; Source; Therapeutic; Therapeutic Index; Toxic effect; United States National Institutes of Health; base; drug clearance; experience

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. Daunomycin is an anthracycline antineoplastic drug widely used in the treatment of acute lymphocytic leukemia and other malignancies in childhood. Like many anticancer agents, daunomycin has a narrow therapeutic index. Doses of anticancer drugs are usually calculated based on body surface area (BSA) or body weight as a uniform standard. This practice is based on the concept that hepatic and renal function are proportionate to BSA. In most studies, however, variability in overall drug clearance is only partially accounted for by variability in BSA. There is a growing list of drugs for which clearance has been poorly correlated with BSA. In addition, after equivalent BSA-based doses, some patients experience little toxicity while others may show severe toxic side effects. Therefore some have questioned whether normalizing anticancer drug dose to BSA is the optimal method for selecting a dosing regimen in adults. Furthermore, the appropriate dosing of anticancer drugs in patients who are very large or who are obese presents a major therapeutic challenge. There is only scanty data on daunomycin pharmacokinetics in children in general, and no data on the effects of overweight or obesity on the pharmacokinetics of daunomycin in children. This study will characterize daunomycin pharmacokinetics and explore the effect of body mass index and body composition on them. A better understanding of the relationships among body size, body composition, and pharmacokinetics could provide a rational approach to the problem of appropriate drug dosing. We hypothesize that body mass index and body composition, as well as age, gender, and ethnic background, will have an impact on the pharmacokinetic behavior of daunomycin, a widely used anticancer agent, in patients 21 years of age and younger. Our primary aim is to determine the pharmacokinetics of daunomycin in children. Secondary aims are to explore the relationship between body composition (percent body fat) and daunomycin pharmacokinetics in children and to determine whether daunomycin pharmacokinetics are correlated with gender, age, ethnic background, or laboratory parameters of renal or hepatic function or white blood count, in children.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 道诺霉素是一种蒽环类抗肿瘤药物，广泛用于治疗儿童急性淋巴细胞白血病和其他恶性肿瘤。与许多抗癌药物一样，道诺霉素的治疗指数较窄。抗癌药物的剂量通常以体表面积（BSA）或体重作为统一标准来计算。这种做法是基于肝肾功能与 BSA 成正比的概念。然而，在大多数研究中，BSA 的变异性只能部分解释总体药物清除率的变异性。越来越多的药物的清除率与 BSA 的相关性较差。此外，在接受同等剂量的 BSA 后，一些患者几乎不会出现毒性反应，而另一些患者可能会出现严重的毒副作用。因此，一些人质疑将抗癌药物剂量标准化为 BSA 是否是选择成人给药方案的最佳方法。此外，对于体型巨大或肥胖的患者，抗癌药物的适当剂量 提出了重大的治疗挑战。一般情况下，关于道诺霉素在儿童中药代动力学的数据很少，也没有关于超重或肥胖对道诺霉素在儿童中药代动力学影响的数据。本研究将表征道诺霉素的药代动力学，并探讨体重指数和身体成分对其的影响。更好地了解体型、身体成分和药代动力学之间的关系可以为适当药物剂量问题提供合理的方法。 我们假设体重指数和身体成分以及年龄、性别和种族背景将对 21 岁及以下患者中广泛使用的抗癌药物道诺霉素的药代动力学行为产生影响。我们的主要目的是确定道诺霉素在儿童中的药代动力学。次要目的是探索儿童身体成分（身体脂肪百分比）与道诺霉素药代动力学之间的关系，并确定道诺霉素药代动力学是否与儿童性别、年龄、种族背景或肾功能、肝功能或白细胞计数的实验室参数相关。