1. Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients
- Author
-
Rima Snariene, Hans Georg Münch, Anne Smits, Christopher M. Rubino, Arunas Liubsys, Karine Litherland, Tomasz Tomasik, Kamal Hamed, Dace Gardovska, Chi D. Hornik, Mark J Polak, Przemko Kwinta, Veerle Cossey, Sebastian Schröpf, Christine Ruehle, and Miroslava Bosheva
- Subjects
Data Analysis ,Male ,PNEUMONIA ,cephalosporin ,Cephalosporin ,Phases of clinical research ,Pediatrics ,THERAPY ,Gastroenterology ,Medicine ,noncompartmental analysis ,Child ,Cross Infection ,pediatric patients ,Half-life ,SPECTRUM CEPHALOSPORIN BAL5788 ,Anti-Bacterial Agents ,Community-Acquired Infections ,Infectious Diseases ,Child, Preschool ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Administration, Intravenous ,Female ,Life Sciences & Biomedicine ,pharmacokinetics ,ceftobiprole ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Immunology ,Ceftobiprole ,DOSE PHARMACOKINETICS ,Antimicrobial Reports ,Microbial Sensitivity Tests ,Minimum inhibitory concentration ,Pharmacokinetics ,Internal medicine ,Humans ,Dosing ,Science & Technology ,business.industry ,Infant, Newborn ,Infant ,Pneumonia ,PHARMACODYNAMICS ,medicine.disease ,Cephalosporins ,Pediatrics, Perinatology and Child Health ,business - Abstract
Supplemental Digital Content is available in the text., Background: Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pneumonia. Methods: Noncompartmental pharmacokinetics and safety were analyzed from 2 recently completed pediatric studies, a single-dose, phase 1 study in neonates and infants up to 3 months of age (7.5 mg/kg) and a phase 3 study in patients 3 months to 17 years of age with pneumonia (10–20 mg/kg with a maximum of 500 mg per dose every 8 hours for up to 14 days). Results: Total ceftobiprole plasma concentrations peaked at the end of infusion. Half life (median ranging from 1.9 to 2.9 hours) and overall exposure (median AUC ranging from 66.6 to 173 μg•h/mL) were similar to those in adults (mean ± SD, 3.3 ± 0.3 hours and 102 ± 11.9 μg•h/mL, respectively). Calculated free-ceftobiprole concentrations in the single-dose study remained above a minimum inhibitory concentration (MIC) of 4 mg/L (fT > MIC of 4 mg/L) for a mean of 5.29 hours after dosing. In the pneumonia study, mean fT > MIC of 4 mg/L was ≥5.28 hours in all dose groups. Ceftobiprole was well tolerated in both studies. Conclusions: Pharmacokinetic parameters of ceftobiprole characterized in the pediatric population were within the range of those observed in adults. In the pneumonia study, the lowest percentage of the dosing interval with fT > MIC of 4 mg/L was 50.8%, which suggests that pharmacokinetic-pharmacodynamic target attainment can be sufficient in pediatric patients. Ceftobiprole was well tolerated.
- Published
- 2021