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。 daunomycin是一种蒽环类药物，广泛用于治疗儿童期急性淋巴细胞性白血病和其他恶性肿瘤。像许多抗癌剂一样，daunomycin具有狭窄的治疗指数。抗癌药物的剂量通常是根据身体表面积（BSA）或体重作为统一标准来计算的。这种做法基于肝功能和肾功能与BSA成比例的概念。但是，在大多数研究中，总体药物清除的变异性仅由BSA的变异性部分解释。越来越多的药物清单与BSA相关。此外，在基于BSA的剂量之后，有些患者几乎没有毒性，而另一些患者可能显示出严重的毒性副作用。因此，有些人质疑将抗癌药剂量归一化为BSA是否是选择成人剂量方案的最佳方法。此外，适当的抗癌药物在很大或肥胖的患者中的适当给药 提出一个重大的治疗挑战。一般而言，儿童中只有关于多霉素药代动力学的数据很少，并且没有关于超重或肥胖对儿童药代动力学的影响的数据。这项研究将表征Daunomycin药代动力学，并探索体重指数和身体成分对它们的影响。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的药物给药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岁及以下的患者多诺莫霉素（一种广泛使用的抗癌剂）的药代动力学行为产生影响。我们的主要目的是确定儿童多霉素的药代动力学。次要目的是探索儿童中身体成分（人体脂肪百分比）和daunomycin药代动力学之间的关系，并确定daunomycin药代动力学是否与性别，年龄，种族背景或肾功能或肝功能或白血球的性别，年龄，种族背景或实验室参数相关。