SPR720 is a phosphate ester prodrug that is converted rapidly
in vivo
to SPR719, the active moiety, which exhibits potent
in vitro
activity against clinically relevant mycobacterial species including
Mycobacterium avium
complex (MAC) and
Mycobacterium abscessus
. SPR720 is in clinical development for the treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) due to MAC. This study evaluated the safety and the intrapulmonary pharmacokinetics of SPR719 in healthy volunteers. A total of 30 subjects received oral SPR720 1,000 mg once daily for 7 days followed by bronchoscopy and bronchoalveolar lavage, with blood samples collected for plasma pharmacokinetic assessments. Mean SPR719 area under the concentration-time curve from time 0 to 24 hours (AUC
0–24
) and maximum concentration (
C
max
) for plasma, epithelial lining fluid (ELF), and alveolar macrophages (AM) were 52,418 ng·h/mL and 4,315 ng/mL, 59,880 ng·h/mL and 5,429 ng/mL, and 128,105 ng·h/mL and 13,033 ng/mL, respectively. The ratios of ELF to total plasma concentrations of SPR719 based on AUC
0–24
and
C
max
were 1.14 and 1.26, and the ratios of AM to total plasma concentrations of SPR719 based on AUC
0–24
and
C
max
were 2.44 and 3.02, respectively. When corrected for protein binding, the ratios of ELF to unbound plasma concentrations of SPR719 for AUC
0–24
and
C
max
were 19.87 and 21.88, and the ratios of AM to unbound plasma concentrations of SPR719 for AUC
0–24
and
C
max
were 42.50 and 52.53, respectively. No unexpected safety findings were observed. Results from this study of the intrapulmonary disposition of SPR719 support further investigation of SPR720 as a potential oral agent for the treatment of patients with NTM-PD.
CLINICAL TRIALS
This study is registered with
ClinicalTrials.gov
as
NCT05955586
.