Journal: Antimicrobial Agents and Chemotherapy

Article Title: Epetraborole pharmacokinetics/pharmacodynamics in the hollow fiber system model of Mycobacterium tuberculosis

doi: 10.1128/aac.00481-25

Figure Lengend Snippet: Epetraborole exposure-response relationship in the HFS-TB. ( A ) Curve fitting for each sampling day based on the CFU/mL readouts. ( B ) Curve fitting for each sampling day based on the MGIT-derived TTP readouts. ( C ) Comparison of EC 80 values calculated using CFU/mL and TTP-derived readouts. ( D ) Exposure-dependent epetraborole antimicrobial resistance in the HFS-TB. (MGIT, Mycobacteria Growth Indicator Tube).

Article Snippet: Finally, we used the recently published Monte Carlo experiments (MCE) for epetraborole in silico dose-finding, using the population PK parameters based on Ganesan et al . ( ) (S. Singh, G. D. Boorgula, M. H. Nguyen, et al., unpublished data). shows the AUC 0–24 predicted to be achieved in the epithelial lining fluid (ELF) of doses with oral administration in 10,000 virtual subjects in the MCE. shows that none of the oral doses had a >90% probability of target attainment (PTA) even with twice daily dosing. shows that even with 1,500 mg twice daily intravenous dosing, PTA falls below 90% at an MIC of 0.5 mg/L. shows the cumulative fraction of response (CFR) for the different doses, where the highest intravenous dose achieved a CFR of only 30%.

Techniques: Sampling, Derivative Assay, Comparison

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Epetraborole pharmacokinetics/pharmacodynamics in the hollow fiber system model of Mycobacterium tuberculosis

doi: 10.1128/aac.00481-25

Figure Lengend Snippet: Monte Carlo experiments. ( A ) AUC 0–24 with four different epetraborole doses with two administration routes, using population PK modeling. Notably, the AUCs with different doses overlap due to PK variability. This means that a dose-response study in patients would likely not yield conclusive results, highlighting the translational utility of the in silico approach. ( B ) None of the oral epetraborole doses, irrespective of the dosing schedule, showed >90% PTA. ( C ) Intravenous dosing showed better PTA compared to oral dosing. However, PTA for even the highest dose, 1,500 mg twice a day, falls below 90% at an MIC of 0.5 mg/L. ( D ) CFR for the different doses showing that none of the tested epetraborole doses achieved EC 80 in >90% of patients.

Article Snippet: Finally, we used the recently published Monte Carlo experiments (MCE) for epetraborole in silico dose-finding, using the population PK parameters based on Ganesan et al . ( ) (S. Singh, G. D. Boorgula, M. H. Nguyen, et al., unpublished data). shows the AUC 0–24 predicted to be achieved in the epithelial lining fluid (ELF) of doses with oral administration in 10,000 virtual subjects in the MCE. shows that none of the oral doses had a >90% probability of target attainment (PTA) even with twice daily dosing. shows that even with 1,500 mg twice daily intravenous dosing, PTA falls below 90% at an MIC of 0.5 mg/L. shows the cumulative fraction of response (CFR) for the different doses, where the highest intravenous dose achieved a CFR of only 30%.

Techniques: In Silico