Tedizolid PBPK Predictions Are Compared with Independent Pediatric Data
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.
From Adult Pharmacokinetics to Pediatric Exposure
Researchers at Fujian Medical University Union Hospital and collaborating Chinese institutions developed a physiologically based pharmacokinetic (PBPK) model for tedizolid in GastroPlus using physicochemical and pharmacokinetic parameters from the literature. After comparison with clinical data from healthy adults and adult patients, the model was scaled to ages 2–18 years using age-dependent physiology.
Pediatric predictions were assessed against independent clinical data. All predicted AUC and peak-concentration values fell within a twofold error range, and most measured concentrations were within the model’s 90% prediction interval.
Simulated Regimens and Their Target
The researchers then simulated once-daily intravenous and oral regimens for immunocompetent patients. The target was a free-drug AUC-to-minimum-inhibitory-concentration ratio of at least 3, with a target-attainment probability of at least 90%.
At a minimum inhibitory concentration of 0.5 mg/L, simulated doses of at least 4 mg/kg met that probability target in children aged 2 to under 12 years. For ages 12 to under 18 years, a fixed 200 mg dose or 3 mg/kg met the same target by either route. These are model-derived candidate regimens for further clinical evaluation.