TABLE 2.
Summary of GEP human urine exposures and nonclinical in vitro PK/PD targetse
| Item (reference[s]) | AUC24 (μg · h/mL)a | fAUC0–24/MIC ratio |
|---|---|---|
| Efficacy target (fAUC0–24/MIC magnitude required for a 1-log reduction in bacterial burden) from E. coli in vitro PK/PD model (30) | – | 41.3 |
| Resistance suppression target from a 10-day E. coli hollow-fiber infection model (30) | – | 275 |
| Minimum urine exposure from healthy volunteers following single oral dose of GEP at 1,500 mg BID (35, 40) | 1,614b | 403a,c |
| Steady-state (day 4) minimum urine concn from participants with uUTId following oral GEP at 1,500 mg BID for 5 days (total of 10 doses) (8) | 4,512 | 1,128a,c |
a
Protein binding adjustment was not required for urine. –, not applicable.
b
Calculated from a minimum urine AUC12 of 807 μg · h/mL.
c
A GEP MIC of 4 μg/mL was applied (gepotidacin MIC90 against fluoroquinolone-resistant E. coli) (15).
d
Twenty-two participants were evaluated (8).
e
AUC, area under the concentration-time curve; BID, twice daily; GEP, gepotidacin; PD, pharmacodynamics; PK, pharmacokinetics; uUTI, uncomplicated urinary tract infection.