Model-Based Approach for Optimizing Ceftobiprole Dosage in Pediatric Patients.

Ceftobiprole is an advanced-generation cephalosporin for intravenous administration with activity against Gram-positive and Gram-negative organisms. A population pharmacokinetic (PK) model characterizing the disposition of ceftobiprole in plasma using data from patients in three pediatric studies was developed. Model-based simulations were subsequently performed to assist in dose optimization for the treatment of pediatric patients with hospital-acquired or community-acquired pneumonia. The population PK data set comprised 518 ceftobiprole plasma concentrations from 107 patients from 0 (birth) to 17 years of age. Ceftobiprole PK was well described by a three-compartment model with linear elimination. Ceftobiprole clearance was modeled as a function of glomerular filtration rate; other PK parameters were scaled to body weight. The final population PK model provided a robust and reliable description of the PK of ceftobiprole in the pediatric study population. Model-based simulations using the final model suggested that a ceftobiprole dose of 15 mg/kg of body weight infused over 2 h and administered every 12 h in neonates and infants <3 months of age or every 8 h in older pediatric patients would result in a ceftobiprole exposure consistent with that in adults and good pharmacokinetic-pharmacodynamic target attainment. The dose should be reduced to 10 mg/kg every 12 h in neonates and infants <3 months of age who weigh <4 kg to avoid high exposures. Extended intervals and reduced doses may be required for pediatric patients older than 3 months of age with renal impairment.