Dataset Information

Pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose intravenous ceftobiprole in healthy Chinese participants.

ABSTRACT:

Background

Ceftobiprole is a novel β-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 β-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.

SUBMITTER: Li WZ

PROVIDER: S-EPMC8263851 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose intravenous ceftobiprole in healthy Chinese participants.

Li Wan-Zhen WZ Wu Hai-Lan HL Chen Yuan-Cheng YC Guo Bei-Ning BN Liu Xiao-Fen XF Wang Yu Y Wu Ju-Fang JF Zhang Jing J

Annals of translational medicine 20210601 11

<h4>Background</h4>Ceftobiprole is a novel β-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.<h4>Methods</h4>The use of ceftobiprole was investigated in ...[more]

PMID: 34350251

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Project description:Relebactam/imipenem/cilastatin is approved in the United States to treat complicated urinary tract and intra-abdominal infections in patients who have limited or no alternative treatment options and hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP). Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian participants. This study evaluated the pharmacokinetics, safety, and tolerability of relebactam/imipenem/cilastatin in 12 healthy Chinese participants after three single doses of increasing concentrations (relebactam at 125, 250, or 500 mg; cilastatin at 250, 500, or 1,000 mg; and imipenem at 250, 500, or 1,000 mg) and after multiple doses every 6 h of a single concentration (relebactam at 250 mg, cilastatin at 500 mg, and imipenem at 500 mg) for 14 days. After single doses, the area under the concentration-time curve (AUC) extrapolated to infinity (relebactam, 15.0 to 70.7 h · mg/liter; imipenem, 24.1 to 109.8 h · mg/liter; cilastatin, 18.4 to 95.3 h · mg/liter) and the AUC from 0 to 6 h (relebactam, 14.2 to 66.3 h · mg/liter; imipenem, 23.4 to 107.3 h · mg/liter; cilastatin, 18.3 to 94.4 h · mg/liter) increased in a dose-dependent manner; clearance (relebactam, 6.9 to 8.3 liters/h; imipenem, 8.6 to 10.4 liters/h; cilastatin, 10.5 to 13.6 liters/h) and half-life (relebactam, 1.4 to 1.6 h; imipenem, 1.0 to 1.2 h; cilastatin, 0.7 to 1.0 h) were consistent between doses. Pharmacokinetic parameters after multiple doses were similar to parameters after a single dose (geometric mean ratios of 0.8 to 1.0 for all three agents). Relebactam/imipenem/cilastatin was well tolerated; mild adverse events occurred during single dosing, and one participant experienced serious adverse events after multiple doses. Pharmacokinetics and safety data are comparable with data from participants of other ethnicities, supporting the use of relebactam/imipenem/cilastatin at the approved dose and schedule in Chinese patients.

Dataset Information

Pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose intravenous ceftobiprole in healthy Chinese participants.

Background

Methods

Results

Conclusions

Publications

Pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose intravenous ceftobiprole in healthy Chinese participants.

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