Plasma and intrapulmonary pharmacokinetics of cefepime and taniborbactam in healthy adult participants

Cefepime-taniborbactam is being developed for the treatment of serious multidrug-resistant (MDR) Gram-negative bacterial infections. This study determined and compared plasma and epithelial lining fluid (ELF) concentrations of cefepime and taniborbactam in 30 healthy adult participants. The dosing regimen was 2 g cefepime/0.5 g taniborbactam administered as a 4 h intravenous infusion every 8 h for a total of six doses. Mean plasma and ELF concentration values with the four aspirates at each bronchoalveolar lavage (BAL) sampling time (1, 3, 4.25, 5, 6, and 8 h) were used to estimate the area under the concentration-time curve (AUC_0-8). The mean AUC_0-8 values of unbound plasma concentrations of cefepime and taniborbactam were 262.2 and 84.77 µg·h/mL, respectively. The drug penetration ratios of ELF to unbound plasma concentrations (DPR_ELF/plasma) were based on the AUC_0-8 values of six different BAL aspirate calculations: single aspirates (for the first, second, third, and fourth BAL sample) and pooled aspirates (BAL samples 2+3+4 and 1+2+3+4). The AUC_0-8 values for ELF for individual and pooled aspirates ranged from 51.62 to 97.86 µg·h/mL for cefepime and 13.14 to 21.69 µg·h/mL for taniborbactam. The DPR_ELF/plasma ranged from 0.197 to 0.373 for cefepime and 0.153 to 0.253 for taniborbactam and was dependent on which aspirate of recovered BAL fluid was used. The highest and lowest values of AUC_0-8 values for ELF and DPR_ELF/plasma for cefepime and taniborbactam were observed with aspirate 1 and aspirate 4, respectively. These results support further consideration of cefepime-taniborbactam as a potential treatment for bacterial pneumonia caused by susceptible MDR Gram-negative pathogens.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04951505.