PhD defence

Quantitative Pharmacology Approaches to Inform Treatment Strategies Against Tuberculosis

• K.J. Mehta

Date

Thursday 30 May 2024

Time

13:45 - 14:30 hour

Address

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof. C. van Hasselt
• Prof. P. van der Graaf

Summary

Tuberculosis (TB) is associated with high morbidity and mortality. Current key challenges against treatment of TB include variability in treatment response, evasion of host immune response, and development of drug resistance. Quantitative pharmacology methods are valuable tools for developing innovative approaches to optimize treatment against Mtb infections to address the challenges effectively and efficiently.

Several takeaways were derived from this work. For instance, physiologically-based pharmacokinetic (PBPK) model-based predictions of target site exposures after accounting for intrinsic and extrinsic factors affecting interindividual variability in pharmacokinetic (PK) can be useful to optimize dosing schedules anti-TB drugs to attain optimal Mtb killing.

PBPK models are also well suited to understand tissue distribution and binding characteristics of drugs enabling translational prediction of a drug's viability for treating different forms of TB, including pulmonary TB and TB meningitis. Similarly, quantitative frameworks, e.g., bedaquiline, pretomanid, and linezolid  combination (BPaL) framework, can be useful to develop new combination regimens and to evaluate treatment optimization approaches for combination regimens against TB, especially drug-resistant TB.

Moreover, we discussed leveraging host-pathogen interactions for treatment of TB and showcased the use of quantitative systems pharmacology (QSP) for evaluating adjunctive host-directed therapies (HDTs) for TB treatment.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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