ABTR06C1 PHARMACOKINETICS OF DAUNOMYCIN IN CHILDREN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 柔红霉素是一种蒽环类抗生素，广泛用于治疗儿童急性淋巴细胞白血病和其他恶性肿瘤。像许多抗癌药物一样，柔红霉素具有狭窄的治疗指数。抗癌药物的剂量通常基于体表面积（BSA）或体重作为统一标准计算。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，总体药物清除率的变异性仅部分归因于BSA的变异性。清除率与BSA相关性较差的药物越来越多。此外，在等效的基于BSA的剂量后，一些患者几乎没有毒性，而另一些患者可能显示出严重的毒副作用。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，对于体型非常大或肥胖的患者， 提出了一个主要的治疗挑战。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，并且没有关于超重或肥胖对柔红霉素在儿童中的药代动力学影响的数据。本研究将描述柔红霉素的药代动力学特征，并探讨体重指数和身体成分对它们的影响。更好地了解身体大小，身体成分和药代动力学之间的关系，可以提供一个合理的方法来解决问题的适当的药物剂量。 我们假设体重指数和身体成分，以及年龄，性别和种族背景，将对柔红霉素，广泛使用的抗癌药物，在21岁及以下的患者的药代动力学行为的影响。我们的主要目的是确定柔红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（体脂百分比）与柔红霉素药代动力学之间的关系，并确定柔红霉素药代动力学是否与儿童的性别、年龄、种族背景或肾或肝功能或白色血细胞计数的实验室参数相关。

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.