Population Pharmacokinetic Modeling and Probability of Target Attainment Analyses in Asian Patients With Community-Acquired Pneumonia Treated With Ceftaroline Fosamil



Li, Jianguo, Das, Shampa ORCID: 0000-0002-2540-4816, Zhou, Diansong and Al-Huniti, Nidal
(2019) Population Pharmacokinetic Modeling and Probability of Target Attainment Analyses in Asian Patients With Community-Acquired Pneumonia Treated With Ceftaroline Fosamil. CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT, 8 (5). pp. 682-694.

[img] Text
Asia CAP PKPD_CPDD .pdf - Author Accepted Manuscript

Download (1MB) | Preview

Abstract

Efficacy of ceftaroline fosamil, the prodrug of the active metabolite ceftaroline, was demonstrated in a phase 3 study of hospitalized Asian patients with Pneumonia Outcomes Research Team (PORT) risk class III-IV community-acquired pneumonia (NCT01371838). The objectives of the current analysis were to expand an existing ceftaroline and ceftaroline fosamil population pharmacokinetic (PK) model with data from this phase 3 study and a phase 1 study (NCT01458743) assessing ceftaroline PK in healthy Chinese volunteers and to evaluate the probability of PK/pharmacodynamic (PK/PD) target attainment (PTA) in Asian patients with community-acquired pneumonia (CAP) treated with ceftaroline fosamil. The ceftaroline plasma concentration-time course was simulated for 5000 Asian patients with CAP for different renal function subgroups using the final model. PTA was calculated for Streptococcus pneumoniae, Staphylococcus aureus, and non-extended-spectrum β-lactamase-producing Enterobacteriaceae. PTA was also evaluated for ceftaroline MIC<sub>90</sub> values of isolates collected from Asia-Pacific surveillance studies (2012-2014) and for EUCAST and FDA/CLSI ceftaroline susceptibility break points. The final model reasonably described the ceftaroline PK. Race was not found to be a significant covariate impacting ceftaroline PK, suggesting similar ceftaroline PK in Asian and Western populations when corrected for body weight. High PTAs (90%-100%) were predicted for Asian patients with CAP treated with ceftaroline fosamil, covering MIC<sub>90</sub> values of target CAP pathogens from the region. Similarly, >90% PTAs were predicted at EUCAST and FDA/CLSI clinical break points for these pathogens. These results support the use of the ceftaroline fosamil dosing regimens approved in Europe and the United States in Asian patients with PORT III-IV CAP.

Item Type: Article
Uncontrolled Keywords: ceftaroline fosamil, community-acquired pneumonia, population pharmacokinetics, probability of target attainment, PK, PD
Depositing User: Symplectic Admin
Date Deposited: 03 May 2019 10:37
Last Modified: 18 Sep 2023 17:56
DOI: 10.1002/cpdd.673
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3039353