Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Center on Obesity Management and Prevention, Stanley Manne Children's Research Institute, Chicago, Illinois, USA.
Clin Transl Sci. 2021 Mar;14(2):509-517. doi: 10.1111/cts.12896. Epub 2020 Nov 22.
Obesity is a prevalent childhood condition and the degree of adiposity appears likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. We undertook these studies to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. We examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. Additionally, we conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. BF% was correlated with body mass index (BMI), but was highly variable among both children with healthy body weights and those with obesity. Bio-impedance and several demographically derived techniques produced mean estimates of BF% that differed from dual x-ray absorptiometry by < 1% (accuracy) and a SD of 5% or less (precision). Simulation studies confirmed that when the differences in precision among the several methods were small compared with unexplained between-subject variability of a PK parameter, the techniques were of similar value in assessing the contribution of BF%, if any, as a covariate for that PK parameter. The combination of sex and obesity stage explained 68% of the variance of BF% with BMI. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.
肥胖是一种普遍的儿童疾病，体脂程度似乎是许多药物药代动力学（PKs）的重要协变量。我们进行了这些研究，以促进评估，在适当的情况下，量化体脂肪百分比（BF％）对儿童 PK 参数的协变量影响。我们检查了两个大型数据库，以确定体重健康的儿童和肥胖儿童的 BF％值和可变性，并比较了临床方法和基于人口统计学的技术对 BF％估计的准确性和精密度。此外，我们进行了模拟研究，以评估几种方法在临床试验中的应用效果。BF％与体重指数（BMI）相关，但在体重健康的儿童和肥胖儿童中均具有高度可变性。生物阻抗和几种基于人口统计学的技术产生的 BF％平均估计值与双能 X 射线吸收法相差<1％（准确性），标准差为 5％或更小（精密度）。模拟研究证实，当几种方法之间的精度差异与 PK 参数的未解释个体间变异性相比较小时，这些技术在评估 BF％作为该 PK 参数的协变量的贡献方面具有相似的价值。性别和肥胖阶段的组合可以解释 BF％与 BMI 之间 68％的方差。可以从性别和肥胖阶段常规估算 BF％，以评估 BF％作为潜在协变量的贡献。
