Dose Optimization of Cefazolin for Pediatric Patients with Renal Impairment Using Physiologically Based Pharmacokinetic Modeling (PBPK) in GastroPlus

Background/Objectives: Cefazolin is a first-generation cephalosporin antibiotic widely used for the treatment and prophylaxis of bacterial infections in both adult and pediatric populations. It is predominantly eliminated unchanged by the kidneys. Impaired renal function can reduce its clearance and increase systemic exposure. This study aimed to develop and validate a PBPK model of cefazolin using GastroPlus™ 9.9 to optimize dosing in pediatric patients with renal impairment.

Methods

A cefazolin PBPK model incorporating renal transport processes was developed using clinical data from healthy adults, subsequently evaluated in adults with renal impairment, and scaled to healthy pediatrics following validation in these populations. The model was extrapolated to pediatric patients with varying degrees of renal impairment. Dose optimization was performed based on predicted exposure, followed by pharmacodynamic evaluation using unbound fractions and a selected MIC of 4 µg/mL.