Pharmacokinetics of single‐dose ceftaroline fosamil in children with cystic fibrosis

Background Single‐dose pharmacokinetics (PK) and safety of ceftaroline fosamil with population pharmacokinetic/pharmacodynamic (PK/PD) modeling for staphylococcal pneumonia was performed in children with CF. Methods Subjects between 6 and 18 years old were evaluated in this phase 1, open‐label, single‐dose, prospective study using 10 mg/kg (up to 600 mg). Non‐compartmental analysis and population‐based PK analyses with Monte Carlo simulation (for doses 8‐20 mg/kg every 8 h, infused over 1‐4 h) were conducted. Results A total of 20 subjects were enrolled. The median age and weight were 12 yr (range 6.3‐17.4) and 38.7 kg (range 17.8‐94.3), respectively. A 3‐compartment linear model incorporating age and weight provided the best fit for the data. Comparing children 6 to <12 years to those 12 to <18 years, the mean posthoc Bayesian parameter estimates for total volume of distribution (V T ) were 0.32 ± 0.05 L/kg versus 0.32 ± 0.04 L/kg, P  = 0.7; and total Clearance (CL T ), 0.50 ± 0.10 L/h/kg versus 0.30 ± 0.07 L/h/kg, P  = 0.001. Using susceptibility data from pediatric MRSA lower respiratory tract isolates, 8 mg/kg (maximum of 1000 mg per dose) infused over 1 h every 8 h achieved free‐drug plasma concentrations above the minimum inhibitory concentration for ≥60% of the dosing interval in at least 95% of virtual subjects. Conclusions Since children with CF have increased ceftaroline CL compared with published data from non‐CF children; greater dosages may be required in children with CF to achieve adequate exposure in the treatment of MRSA pneumonia. Pharmacodynamic‐based dosing predicts that dosing should also be based on the patient's MRSA MIC.