Objectives
Tuberculosis (TB), one of the deadliest infectious diseases worldwide [1], still requires therapy optimization to eradicate Mycobacterium tuberculosis residing in hard-to-treat granuloma lesions. Bacterial clearance is impacted by drug diffusion through the cellular lesion surrounding the non-vascularized caseum; therefore, drug penetration is a key determinant of treatment efficacy and pharmacodynamic target attainment (TA). Combining experimental data from anti-TB treatments in rabbit models with simulation tools can support the identification of the most effective treatments for eradicating M. tuberculosis infection [2]. Here, we present a study of 16 anti-TB drugs, focusing on their penetration kinetics into the cellular lesion and caseum by extending and adapting a published minimal physiologically based pharmacokinetic (mPBPK) mouse model [2] to TB-infected rabbits.
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