CLINICAL TRIAL: OPTIMIZING PAIN TREATMENT IN PRE-TERM NEONATES

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。 认识到新生儿会经历疼痛，导致在新生儿重症监护病房更普遍地使用吗啡。有数据表明，在使用吗啡时，需要考虑其代谢和药代动力学(PK)的发展模式。然而，这些信息还没有转化为承认药物处置和作用的差异的新生儿吗啡剂量计划。本研究的目的是：1)评估发育阶段(由孕期和出生后年龄定义)与UGT2B7活性的关系(以血和尿中M3G/吗啡和M6G/吗啡比值来衡量)；2)评估UGT2B7基因变异性与血和尿中M6G/吗啡和M3G/吗啡比值的关系；3)评估肾小球滤过率与M6G/吗啡比率、M3G/吗啡比率以及血和尿中吗啡浓度的关系；4)评估阿片受体和儿茶酚-O-甲基转移酶(COMT)基因变异与吗啡临床反应的关系；5)建立了基于胎龄、出生后年龄、肾小球滤过率和UGT2B7基因、阿片受体基因和COMT基因变异的吗啡给药群体PK/PD模型。

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. The recognition that pain is experienced by neonates has led to the more common use of morphine in neonatal intensive care units. There are data demonstrating a developmental pattern in the metabolism and pharmacokinetics (PK) of morphine that needs to be considered in its use. This information, however, has not been translated into a morphine dosage schedule for neonates that recognizes differences in both drug disposition and action. The purpose of this study is to 1) evaluate the relationship of developmental stage (defined by both gestational and postnatal age) to UGT2B7 activity (as measured by the M3G/morphine ratio and M6G/morphine ratio in blood and urine); 2) evaluate the relationship of UGT2B7 genetic variability to the M6G/morphine ratio and the M3G/morphine ratio in both blood and urine; 3) evaluate the relationship of glomerular filtration rate to M6G/morphine ratio, M3Gmorphine ratio, and morphine concentrations in both blood and urine; 4) evaluate the relationship of ¿-opioid receptor variability and catechol-O-methyltransferase gene (COMT) variability to clinical response following administration of morphine; and 5) develop a population PK/PD model of morphine dosing based on gestational age, postnatal age, glomerular filtration rate, and genetic variability in UGT2B7, in the ¿-opioid receptor, and in COMT.