Abstract
ABSTRACTCeftobiprole 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.
Highlights
Ceftobiprole is an advanced-generation cephalosporin for intravenous administration with activity against Gram-positive and Gram-negative organisms
Three quantifiable samples from Study CSI-1006 were deemed outliers based on a conditional weighted residual (CWRES) of .3; one of these samples was obtained from a patient who had only one evaluable sample, and that patient was excluded from the analysis
While those analyses provided important information regarding ceftobiprole exposure in the individual patients at the specific doses used in the studies, model-independent methods are limited in terms of evaluating alternative dosing regimens that may be more appropriate for clinical use
Summary
Ceftobiprole is an advanced-generation cephalosporin for intravenous administration with activity against Gram-positive and Gram-negative organisms. Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation cephalosporin for intravenous (i.v.) administration, with broad-spectrum activity against Gram-positive and Gram-negative organisms, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus, penicillin-resistant Streptococcus pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa [1,2,3] It is approved in many European and other countries for the treatment of hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia, and community-acquired pneumonia (CAP) [4]. The PK data from Studies CSI-1006, BPR-PIP-001, and BPR-PIP-002 were used to establish a pediatric population PK model for ceftobiprole, and the analyses described were designed to support the optimal dosing regimens of ceftobiprole for pediatric patients with HAP or CAP
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
