Intrapulmonary Pharmacokinetic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Patients With Pneumonia and Healthy Subjects.
Cefiderocol is a siderophore cephalosporin for the treatment of infections caused by gram‐negative bacteria including carbapenem‐resistant strains. The aim of this study was to develop an intrapulmonary pharmacokinetic (PK) model of cefiderocol and assess the PK profile in lungs. An intrapulmonary P...
| Publicado en: | Journal of Clinical Pharmacology Vol. 62; no. 5; pp. 670 - 681 |
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| Autores principales: | , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
May2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=156223895&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 156223895 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: May2022 vid: 62 iid: 5 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 156223895 155426620 156223895 156223895 10.1002/jcph.1986 156223895 ppf: 670 ppct: 11 formats: tig: atl: Intrapulmonary Pharmacokinetic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Patients With Pneumonia and Healthy Subjects. aug: au: Kawaguchi, Nao Katsube, Takayuki Echols, Roger Wajima, Toshihiro Nicolau, David P. affil: Clinical Pharmacology & Pharmacokinetics, Shionogi & Co., Ltd., Osaka,, Japan sug: subj: Pneumonia Drug Therapy Cephalosporins Pharmacokinetics Chelating Agents Pharmacokinetics Research Subjects Human Respiration, Artificial Epithelial Cells Body Fluids Simulations Comparative Studies Systems Analysis Microbial Culture and Sensitivity Tests Descriptive Statistics ab: Cefiderocol is a siderophore cephalosporin for the treatment of infections caused by gram‐negative bacteria including carbapenem‐resistant strains. The aim of this study was to develop an intrapulmonary pharmacokinetic (PK) model of cefiderocol and assess the PK profile in lungs. An intrapulmonary PK model of cefiderocol was developed using the concentration data in plasma and epithelial lining fluid (ELF) from 7 patients with pneumonia requiring mechanical ventilation and 20 healthy subjects. Subsequently, the model was applied to assess the ELF exposure of 125 patients with nosocomial pneumonia. Monte Carlo simulations were performed to calculate the probability of target attainment for the percentage of time for which free ELF concentrations exceed the minimum inhibitory concentration (MIC) over the dosing interval (%fT>MIC,ELF). The developed model adequately described ELF concentrations and suggested the delayed distribution in ELF for patients with pneumonia compared to healthy subjects. Lung penetration ratio of cefiderocol in patients with pneumonia was calculated to be 34%, which was 1.4‐fold that in healthy subjects. The estimated %fT>MIC,ELF was 100% in most of patients with nosocomial pneumonia, and no PK/pharmacodynamic relationship with %fT>MIC,ELF was found for microbiological or clinical outcome. The probability of target attainment for 100% fT>MIC,ELF was ≥ 99.5% against MICs ≤2 μg/mL and ≥87.0% against MICs ≤4 μg/mL regardless of renal function. The median of simulated ELF trough concentrations at steady state was >4 μg/mL regardless of renal function. These results reveal the adequacy of cefiderocol exposure in plasma and ELF at the recommended dosing regimens adjusted on the basis of renal function in critically ill patients with pneumonia. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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