Daniele Boaretti at PAGE 2026
Tuberculosis (TB) remains one of the world’s deadliest infectious diseases, with treatment success often limited by the ability of drugs to reach the complex granuloma lesions where Mycobacterium tuberculosis can persist. Improving our understanding of drug penetration into these difficult-to-treat compartments is essential for developing more effective therapies.
At the Population Approach Group Europe (PAGE) Meeting 2026 in Dubrovnik, Croatia, COSBI researcher Daniele Boaretti presented the poster “A lesion-centric extension of a minimal PBPK model to predict anti-tuberculosis drug target attainment in rabbits.”
The work extends a previously developed minimal physiologically based pharmacokinetic (mPBPK) framework by explicitly representing two key components of TB granulomas: the cellular lesion and the caseum. The resulting lesion-centric model was calibrated using experimental data from 16 anti-tuberculosis compounds measured in plasma, lung tissue, cellular lesions and caseum in TB-infected rabbits.
By combining experimental measurements with mechanistic modeling, the framework enables the prediction of tissue-specific drug exposure and target attainment directly at the site of infection. The results highlight substantial differences in lesion and caseum penetration across drugs and treatment regimens, providing a quantitative tool for comparing therapeutic strategies and identifying compounds with the greatest potential to eradicate persistent bacterial populations.
Beyond evaluating individual drugs, the model supports the optimization of multidrug regimens and represents a step toward mechanism-based prioritization of therapies aimed at sterilizing caseous lesions, one of the major challenges in tuberculosis treatment.
This research reflects COSBI’s ongoing commitment to advancing model-informed drug development through the integration of computational modeling, pharmacology and translational research.
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Digital copies of selected posters are available upon request at info@cosbi.eu.
