Pharmaceutics
Optimized Flomoxef Dosing Strategy for Extended-Spectrum Beta-Lactamase-Producing Bacteria, Based on Pooled Pharmacokinetic and Pharmacodynamic Analysis
By Tetsushu Onita, Yui Sano, Nami Kuruma and 5 others.
Abstract
Background
Flomoxef exhibits antibacterial activity against extended-spectrum beta-lactamase (ESBL)-producing bacteria and is a potential alternative to carbapenems. However, its pharmacokinetic (PK) characteristics remain unclear, and the appropriate minimum inhibitory concentration (MIC) breakpoint for flomoxef remains controversial. This study aimed to develop a flomoxef PK model using pooled meta-analysis and to evaluate various dosing regimens for ESBL-producing bacterial infections.
Methods
Flomoxef concentration data were systematically collected from PubMed and J-STAGE. PK modeling of flomoxef was performed using the collected serum concentration data with NONMEM 7.5. Patient characteristics were examined as covariates for clearance and volume of distribution. For stochastic PK/pharmacodynamic (PD) simulation, the probability of attaining the PK/PD target {70% free time above the MIC [fT > MIC]} was calculated. The target MIC was determined by systematically reviewing flomoxef susceptibility data for ESBL-producing bacteria across different regions.