Module232025

09/05/2025

Scaling of PK/PD knowledge to paediatrics

Preliminary predictive simulation of drug PK/PD behaviour in paediatrics

A bsorption

D istribution

A bsorption

D istribution

Not to replace clinical studies but

Drug exposure

Drug exposure

PK

M etabolism

E xcretion

M etabolism

E xcretion

Studies are confirmatory rather than exploratory

Target (Access to effect site) Effect (Drug-receptor)

Guidance in study design

Target (Access to effect site)

PD

Effect (Drug-receptor)

Dose Efficient sampling

↓ studies

↓ n

The Organisation for Professionals in Regulatory Affairs

25

Allometric scaling

• Allometric-based model for weight (BW) applied to systemic popPK parameters • Allows a consistent approach to describing data in children older than 2 years of age and adults • Children ≥ 2 years are deemed essentially similar to adults (i.e., mature) and differ only in size • Very useful first approach in those instances when the ADME of the drug has not been fully characterized • Assumption of maturity may not be true for all processes (e.g. active transport)

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PWR=0.75 for CL PWR=1 for V PWR=0.25 for t 1/2

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The Organisation for Professionals in Regulatory Affairs

26