ABTR06C1 PHARMACOKINETICS OF DAUNOMYCIN IN CHILDREN

Baylor College Of Medicine, Houston TX

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Abstract

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.