Pharmacokinetics of Ceftaroline.pdf (1.06 MB)

Pharmacokinetics of ceftaroline in normal body weight and obese (classes I, II, and III) healthy adult subjects.

Download (1.06 MB)
journal contribution
posted on 21.11.2015, 00:00 by JA Justo, SM Mayer, MP Pai, MM Soriano, LH Danziger, RM Novak, KA Rodvold KA
The pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m2 and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of >40 kg/m2 compared to those <30 kg/m2 . A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is >90% when the MIC is <1 g/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at under registration no. NCT01648127.)


This project was an investigator-initiated study supported in part by a grant from Forest Laboratories, Inc. The project utilized services and facilities of the UIC Center for Clinical and Translational Science which is supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1TR000050.


Publisher Statement

This is the copy of an article published in Antimicrobial Agents and Chemotherapy © 2015 American Society for Microbiology Publications.


American Society for Microbiology



Issue date


Usage metrics