ABTR06C1 PHARMACOKINETICS OF DAUNOMYCIN IN CHILDREN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 柔红霉素是一种蒽环类抗肿瘤药物，广泛用于儿童急性淋巴细胞白血病和其他恶性肿瘤的治疗。像许多抗癌药物一样，柔红霉素的治疗指数很窄。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。这种做法是基于肝和肾功能与BSA成比例的概念。然而，在大多数研究中，总体药物清除量的可变性仅部分地被BSA的可变性所解释。越来越多的药物清单上的清除与BSA的相关性很差。此外，在基于BSA的等量剂量后，一些患者几乎没有毒性，而另一些患者可能表现出严重的毒副作用。因此，一些人质疑将抗癌药物剂量正常化到BSA是否是选择成人给药方案的最佳方法。此外，对于体型很大或肥胖的患者，抗癌药物的适当剂量 这是一个重大的治疗挑战。一般来说，关于柔红霉素在儿童中的药代动力学的数据很少，没有关于超重或肥胖对儿童柔红霉素药代动力学影响的数据。本研究将对柔红霉素的药代动力学进行表征，并探讨体重指数和体成分对其的影响。更好地了解人体大小、身体成分和药代动力学之间的关系可以为合理的药物剂量问题提供一种合理的方法。 我们假设体重指数和身体成分，以及年龄、性别和种族背景，将对广泛使用的抗癌药物柔红霉素在21岁及以下患者的药代动力学行为产生影响。我们的主要目的是测定柔红霉素在儿童体内的药代动力学。第二个目的是探讨儿童体内成分(体脂百分比)与柔红霉素药代动力学的关系，并确定柔红霉素在儿童中的药代动力学是否与性别、年龄、民族背景、肾或肝功能或白细胞计数的实验室参数有关。

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.