Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients
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Date
2021-11-01
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Abstract
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.
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Funding Information: C.M.R. is an employee of Institute for Clinical Pharmacodynamics, which received funding for these analyses from Basilea Pharmaceutica International Ltd. A.S.’ research activities are supported by the Clinical Research and Education Council of the University Hospitals Leuven. C.R. and K.L. are employees of, and KH is a consultant for, Basilea Pharmaceutica International Ltd. The other authors have no conflicts of interest to disclose. Publisher Copyright: © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
Keywords
ceftobiprole, cephalosporin, noncompartmental analysis, pediatric patients, pharmacokinetics, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Pediatrics, Perinatology, and Child Health, Microbiology (medical), Infectious Diseases, SDG 3 - Good Health and Well-being
Citation
Rubino, C M, Polak, M, Schröpf, S, Münch, H G, Smits, A, Cossey, V, Tomasik, T, Kwinta, P, Snariene, R, Liubsys, A, Gardovska, D, Hornik, C D, Bosheva, M, Ruehle, C, Litherland, K & Hamed, K 2021, 'Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients', Pediatric Infectious Disease Journal, vol. 40, no. 11, pp. 997-1003. https://doi.org/10.1097/INF.0000000000003296