PMID- 34350251 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220830 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 11 DP - 2021 Jun TI - Pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose intravenous ceftobiprole in healthy Chinese participants. PG - 936 LID - 10.21037/atm-21-588 [doi] LID - 936 AB - BACKGROUND: Ceftobiprole is a novel beta-lactam cephalosporin with activity against Gram-positive and -negative bacteria. The aim of the present study was to investigate the pharmacokinetics (PK), pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerance of ceftobiprole in Chinese participants, to evaluate this dosage regimen for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in China. METHODS: The use of ceftobiprole was investigated in a single-center, open-label, single- and multiple-dose study using 12 healthy Chinese participants (6 males and 6 females). Ceftobiprole plasma and urine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK/PD characteristics of 500 mg ceftobiprole every 8 h at 1.5-, 2-, 3-, or 4-h infusion time were analyzed by Monte Carlo simulations (MCS). RESULTS: The maximum plasma concentration of ceftobiprole was observed 2 h after dosage; its terminal half-life was about 3 h. Ceftobiprole was predominantly eliminated in urine, and the cumulative excretion in 24 h was >90%. There was no accumulation after multiple dosing. Both single and multiple doses were well tolerated, with no severe or serious adverse events (AEs). PK/PD analysis indicated that Staphylococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) were sensitive to ceftobiprole. About half of extended-spectrum beta-lactamase (ESBL) non-producing Enterobacteriaceae are sensitive to ceftobiprole, according to PK/PD results of ceftobiprole. For Pseudomonas aeruginosa (P. aeruginosa), no regimen was found to be effective against strains. CONCLUSIONS: The PK/PD results indicated that 500 mg ceftobiprole every 8 h at 2-h infusion time is expected to achieve good microbiological efficacy in the treatment of CAP and HAP in China. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Li, Wan-Zhen AU - Li WZ AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. FAU - Wu, Hai-Lan AU - Wu HL AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. FAU - Chen, Yuan-Cheng AU - Chen YC AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. AD - Phase I Unit, Huashan Hospital, Fudan University, Shanghai, China. FAU - Guo, Bei-Ning AU - Guo BN AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. FAU - Liu, Xiao-Fen AU - Liu XF AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. FAU - Wang, Yu AU - Wang Y AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. FAU - Wu, Ju-Fang AU - Wu JF AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. AD - Phase I Unit, Huashan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Jing AU - Zhang J AD - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China. AD - Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China. AD - National Health Commission and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. AD - Phase I Unit, Huashan Hospital, Fudan University, Shanghai, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8263851 OTO - NOTNLM OT - Ceftobiprole OT - Monte Carlo simulation (MCS) OT - pharmacokinetic/pharmacodynamic analysis (PK/PD analysis) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-588). The authors have no conflicts of interest to declare. EDAT- 2021/08/06 06:00 MHDA- 2021/08/06 06:01 PMCR- 2021/06/01 CRDT- 2021/08/05 06:31 PHST- 2021/01/08 00:00 [received] PHST- 2021/03/30 00:00 [accepted] PHST- 2021/08/05 06:31 [entrez] PHST- 2021/08/06 06:00 [pubmed] PHST- 2021/08/06 06:01 [medline] PHST- 2021/06/01 00:00 [pmc-release] AID - atm-09-11-936 [pii] AID - 10.21037/atm-21-588 [doi] PST - ppublish SO - Ann Transl Med. 2021 Jun;9(11):936. doi: 10.21037/atm-21-588.