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The allometric exponent for scaling clearance varies with age: A study on seven propofol datasets ranging from preterm neonates to adults

机译:结垢清除的异速指数随年龄变化:从早产儿到成人的七个异丙酚数据集的研究

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Aim For scaling clearance between adults and children, allometric scaling with a fixed exponent of 0.75 is often applied. In this analysis, we performed a systematic study on the allometric exponent for scaling propofol clearance between two subpopulations selected from neonates, infants, toddlers, children, adolescents and adults. Methods Seven propofol studies were included in the analysis (neonates, infants, toddlers, children, adolescents, adults1 and adults2). In a systematic manner, two out of the six study populations were selected resulting in 15 combined datasets. In addition, the data of the seven studies were regrouped into five age groups (FDA Guidance 1998), from which four combined datasets were prepared consisting of one paediatric age group and the adult group. In each of these 19 combined datasets, the allometric scaling exponent for clearance was estimated using population pharmacokinetic modelling (nonmem 7.2). Results The allometric exponent for propofol clearance varied between 1.11 and 2.01 in cases where the neonate dataset was included. When two paediatric datasets were analyzed, the exponent varied between 0.2 and 2.01, while it varied between 0.56 and 0.81 when the adult population and a paediatric dataset except for neonates were selected. Scaling from adults to adolescents, children, infants and neonates resulted in exponents of 0.74, 0.70, 0.60 and 1.11 respectively. Conclusions For scaling clearance, allometric scaling may be of value for scaling between adults and adolescents or children, while it can neither be used for neonates nor for two paediatric populations. For scaling to neonates an exponent between 1 and 2 was identified.
机译:目的对于成人和儿童之间的结垢间隙,通常采用固定指数为0.75的异形结垢。在此分析中,我们对从新生儿,婴儿,学步儿童,儿童,青少年和成人中选出的两个亚群之间异丙酚清除结垢的异速指数进行了系统研究。方法该分析包括七项异丙酚研究(新生儿,婴儿,学步儿童,儿童,青少年,成人1和成人2)。以系统的方式,从六个研究人群中选择了两个,从而得出15个组合数据集。此外,将这七项研究的数据重新分组为五个年龄组(FDA指南1998),从中制备了四个组合数据集,包括一个儿科年龄组和一个成年人组。在这19个组合数据集中的每个数据集中,使用总体药代动力学模型(非标准7.2)估算了清除的异速伸缩比例指数。结果在包括新生儿数据集的情况下,异丙酚清除的异速指数在1.11和2.01之间变化。分析两个儿科数据集时,指数在0.2和2.01之间变化,而当选择成年人口和除新生儿以外的儿科数据集时,指数在0.56和0.81之间变化。从成人扩展到青少年,儿童,婴儿和新生儿,指数分别为0.74、0.70、0.60和1.11。结论对于结垢清除,异体结垢可能对成人,青少年或儿童之间的结垢有价值,而它既不能用于新生儿,也不能用于两个儿科人群。为了缩放到新生儿,确定了1到2之间的指数。

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