Model-Aided Adults-to-Children Pharmacokinetic Extrapolation and Empirical Body Size-Based Dosing Exploration for Therapeutic Monoclonal Antibodies-Is Allometry a Reasonable Choice?

Model-Aided Adults-to-Children Pharmacokinetic Extrapolation and Empirical Body Size-Based Dosing Exploration for Therapeutic Monoclonal Antibodies-Is Allometry a Reasonable Choice? J Clin Pharmacol. 2020 Jun 23;: Authors: Xu Y, Langevin BA, Zhou H, Xu Z Abstract The importance of pharmacokinetic (PK) evaluation in pediatric drug development is well recognized, and a pediatric PK study is generally recommended before pivotal trials to ensure the "right" dose in these studies. The PK of therapeutic monoclonal antibodies (mAbs) is primarily affected by body weight, where adults-to-children extrapolation may conform to allometry. Therefore, PK behavior of mAbs in pediatrics, particularly for those with linear PK, is expected to be predictable based on data in adults. To test this hypothesis, we reviewed published population PK reports of marketed mAbs and assessed model-aided PK extrapolation of mAbs to children (2-17 years) through 5 case studies. For each case study, population PK models were developed based on adult data, with allometric exponents of weight on clearance and volume of distribution fixed as standard values (ie, 0.75 for clearance; 1.0 for volume of distribution), approach 1, or coming from adult model estimates, approach 2. Simulated pediatric PK using these 2 approaches was compared with PK observations in pediatric trials to assess the accuracy in model predictions. For pediatrics 6-17 years, model performance was ge...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research