Module232025

09/05/2025

Semi-physiologic scaling

• Considers developmental changes on those physiological variables involved in drug ADME • Absorption Gastrointestinal function • Distribution Protein binding Blood flows Body composition • Metabolism

Organ blood flows Enzyme ontogeny Organ sizes

• Excretion

Renal function Biliary function • Depending on the extent to which the new drug has been characterized, simplified versions can be used to complement the allometric scaling e.g., inclusion of a correction factor for protein binding

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Optimized study design

• Scaled PK parameters in children of different ages allows to (via simulation): 1. Dose selection aimed at matching adult exposure 2. Optimize the sampling schedule and sample size • Based on the Population Fisher Information Matrix (PFIM) – D-Optimal design maximize the

Rich design EOmpptiimricizeddesign

determinant of the FIM with respect to design variables, to get the lower bound of the covariance matrix of the parameter estimates

Software: ADAPT, PFIM

•

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