In vivo Pharmacokinetics/Pharmacodynamics Profiles for Appropriate Doses of Cefditoren pivoxil against S. pneumoniae in Murine Lung-Infection Model.
Pharm Res
; 40(7): 1789-1797, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37253866
ABSTRACT
PURPOSE:
Cefditoren, the active form of cefditoren pivoxil, is an oral cephalosporin antimicrobial drug. Although cefditoren exhibits high antimicrobial activity against Streptococcus pneumoniae, its pharmacokinetics/pharmacodynamics (PK/PD) characteristics remain unknown. This study aimed to determine its PK/PD parameter with target values for cefditoren against S. pneumoniae in S. pneumoniae lung-infected mice and to simulate MIC range of S. pneumoniae that can be expected to be treated at approved cefditoren doses in human using population pharmacokinetic (PPK) data from patients.METHODS:
Susceptibility testing and time-kill assays against S. pneumoniae ATCC® 49619 were performed for in vitro PD evaluation. Based on the results of a PK study in healthy mice and PD studies in S. pneumoniae lung-infected mice, optimal PK/PD parameters were determined using the correlation curve between the PK/PD parameters and lung bacterial count changes. The target value was calculated to achieve a 2 log10 reduction in the lung bacterial counts.RESULTS:
In vitro PD evaluation showed that cefditoren had a potent antimicrobial effect against S. pneumoniae in a time-dependent manner at concentrations above the MIC. In PK/PD analyses, both fAUC24/MIC and fCmax/MIC were well correlated with bactericidal efficacy, achieving 2 log10-kill with fAUC24/MIC ≥ 63 and fCmax/MIC ≥ 16.CONCLUSIONS:
Cefditoren pivoxil has good therapeutic efficacy against acute pneumonia caused by S. pneumoniae with a MIC ≤ 0.031-0.063 mg/L at approved doses in adults and children.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Infecções Estafilocócicas
/
Anti-Infecciosos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Child
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article