Ceftaroline: An Alternative Broad Spectrum Antibiotic for Pediatric Infections

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2017;23(6) 

In This Article

Pharmacokinetics

Following IV administration of ceftaroline fosamil, peak concentrations of active ceftaroline occur within approximately 5 minutes.[3] The mean maximum concentrations (Cmax) in adults given a 600 mg dose are approximately 32.5 + 4.82 mcg/mL after a 5 minute infusion and 17.4 + 3.87 mcg/mL after a 60 minute infusion. Ceftaroline exhibits little binding to serum proteins (20%) and has a steady state volume of distribution in adults of 20.3 L (range 18.3–21.6 L). It undergoes hydrolysis to an inactive metabolite, with both the remaining unchanged ceftaroline and the M-1 metabolite eliminated by glomerular filtration. The average rate of ceftaroline clearance in adults is 5.56 + 0.20 L/hr. Clearance is prolonged in patients with moderate to severe renal impairment. Hepatic impairment does not appear to have an effect on its clearance.

The pharmacokinetic profile of ceftaroline was evaluated in five pediatric studies. Two were single dose studies; the first was conducted in seven adolescents with normal renal function who received a single 8 mg/kg IV dose. While the volume of distribution and clearance were similar to adult values, the Cmax in the adolescents was 10% lower than adult values and the area under the concentration-time curve (AUC) was 23% lower. A second pharmacokinetic study in children from 28 days to 12 years of age was conducted to guide dosing recommendations for younger children. Three additional studies were performed in conjunction with prospective, randomized, comparator-controlled clinical trials. Serum samples from more than 300 children taking part in these studies were used in a population pharmacokinetic analysis using nonlinear mixed-effects modeling.[6] The results of this pharmacokinetic model confirm the appropriateness of the current dosing recommendations for ceftaroline in the pediatric population.

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