Method Profile
An adult tedizolid model is scaled using age-dependent physiology, assessed against independent pediatric clinical data, and used to compare candidate regimens.
Research assessment of tedizolid exposure and model-derived regimens in immunocompetent patients aged 2–18 years.
A GastroPlus PBPK model with literature-derived drug inputs and age-dependent pediatric physiology.
Adult development and clinical comparison, physiological scaling to childhood, independent pediatric evaluation and regimen simulation.
Drug inputs
Tedizolid physicochemical properties and pharmacokinetic parameters from the literature.
Evaluation data
Clinical pharmacokinetics from healthy adults and adult patients, followed by independent pediatric data.
Population
Ages 2–18 years; intravenous and oral dosing scenarios in immunocompetent patients.
Assess adult and pediatric exposure predictions before comparing candidate regimens against the specified pharmacokinetic/pharmacodynamic target.
Adult clinical evaluation is followed by age-based extrapolation and comparison with independent pediatric data.
Patients aged 2–18 years in the reported independent pediatric pharmacokinetic evaluation.
Observed clinical exposure and concentrations versus adult and pediatric model predictions.
All predicted AUC and peak-concentration values were within twofold error; most observed concentrations were within the 90% prediction interval.
An adult model was scaled using age-related physiology and evaluated in children aged 2–18 years. Predicted AUC and peak concentrations remained within twofold of observed values, supporting further evaluation of simulated pediatric regimens.
