Plasma and intrapulmonary pharmacokinetics of ceftibuten and ledaborbactam in healthy male and female adults

) for aspirate 1 was 14,867 ng·h/mL for CTB and 14,529 ng·h/mL for LED, and for pooled aspirates 2 + 3 + 4 was 10,486 ng·h/mL and 9,809 ng·h/mL, respectively. ELF-to-unbound plasma AUC ratios were 0.341 (aspirate 1) and 0.239 (pooled aspirates 2 + 3 + 4) for CTB and 1.560 and 1.032, respectively, for LED. Participants receiving CTB alone demonstrated similar lung penetration, indicating no effect of LED on CTB exposure. Both CTB/LED-E and CTB alone were safe and well tolerated; all adverse events were mild or moderate and unrelated to study drug. These results demonstrate pulmonary penetration of CTB and LED and support further evaluation of CTB/LED-E for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.This study is registered with ClinicalTrials.gov as NCT06665555.