BACKGROUND AND OBJECTIVE Pharmacokinetic drug-drug interaction (DDI) studies are conducted in adult subjects during drug development but there are limited studies that have characterized pharmacokinetic DDI studies in children. The objective of this study was to evaluate if the DDI clearance values from adults can be allometrically extrapolated from adults to children. METHODS Fifteen drugs were included in this study and the age of the children ranged from premature neonates to adolescents (30 observations across the age groups). The age-dependent exponent (ADE) model was used to predict the clearance of drugs in children from adults following DDI studies. RESULTS The prediction error of drug clearances following DDIs in children ranged from 4 to 67%. Of 30 observations, 17 (57%) and 27 (90%) observations had a prediction error ≤ 30% and ≤ 50%, respectively. CONCLUSION This study indicates that it is possible to predict the clearance of drugs with reasonable accuracy in children from adults following DDI studies using an ADE model. The method is simple, robust, and reliable and can replace other complex empirical models.

中文翻译：

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药物相互作用研究之后的成人儿童清除率的预测：年龄相关指数模型的应用。

背景和目的药代动力学药物相互作用（DDI）研究是在成年受试者中进行的，但是在儿童研究中却很少有以药物动力学DDI研究为特征的研究。这项研究的目的是评估是否可以将成年人的DDI清除值从成年人向儿童进行异速测定。方法本研究包括15种药物，儿童的年龄从早产儿到青少年不等（各年龄段的30个观察结果）。在DDI研究之后，使用年龄依赖性指数（ADE）模型来预测成人儿童中药物的清除率。结果儿童DDIs引起的药物清除率的预测误差为4％至67％。在30个观察结果中，有17个（57％）和27（90％）个观察结果的预测误差≤30％和≤50％，分别。结论本研究表明，使用ADE模型进行DDI研究后，有可能以合理的准确性预测成人儿童的药物清除率。该方法简单，可靠，可靠，可以替代其他复杂的经验模型。