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TBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid. A translational platform incorporating linezolid and BPaL data from preclinical experiments and 4 clinical trials (NCT00396084, NCT02333799, NCT03086486, NCT00816426) is developed, enabling validation of the framework. TBI-223 preclinical and Phase 1 data (NCT03758612) are applied to the translational framework to predict clinical outcomes and optimize TBI-223 dosing in combination with bedaquiline and pretomanid. Results indicate that daily doses of 1200-2400 mg TBI-223 may achieve efficacy comparable to the BPaL regimen, with >90% of patients predicted to reach culture conversion by two months.

Sotorasib exhibits pH‐dependent solubility, making it susceptible to altered exposures when coadministered with acid‐reducing agents (ARAs). Several clinical studies were conducted to investigate the impact of ARAs on sotorasib pharmacokinetics under different clinically relevant scenarios and to identify potential mitigation strategies. Upon coadministration of 960 mg of sotorasib and 40 mg of omeprazole under fasted conditions, sotorasib area under the concentration‐time curve (AUC) and maximum observed plasma concentration (Cmax) decreased approximately 42% and 57%, respectively. Following coadministration with 40 mg of famotidine under fed conditions, sotorasib AUC and Cmax decreased approximately 38% and 35%, respectively. The coadministration of sotorasib and 40 mg of omeprazole under fed conditions led to a 57% and 65% decrease in sotorasib AUC and Cmax, respectively. When sotorasib was coadministered with omeprazole and an acidic beverage compared to sotorasib alone, AUC and Cmax decreased approximately 23% and 32%, respectively, leading to a 19.0 percentage‐point increase in AUC and a 24.6 percentage‐point increase in Cmax for sotorasib when compared to coadministration of sotorasib with omeprazole under fasted conditions. Sotorasib exposure decreased when coadministered with proton pump inhibitors and H2 receptor antagonists. Coadministration with an acidic beverage increased sotorasib exposure upon concomitant administration with omeprazole, which may represent a clinically attractive method to allow ARA use with sotorasib. [ABSTRACT FROM AUTHOR]