A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis.

ABSTRACT: Introduction: Understanding drug exposure at disease target sites is pivotal to profiling new drug candidates in terms of tolerability and efficacy. Such quantification is particularly tedious for anti-tuberculosis (TB) compounds as the heterogeneous pulmonary microenvironment due to the infection may alter lung permeability and affect drug disposition. Murine models have been a longstanding support in TB research so far and are here used as human surrogates to unveil the distribution of several anti-TB compounds at the site-of-action via a novel and centralized PBPK design framework. Methods: As an intermediate approach between data-driven pharmacokinetic (PK) models and whole-body physiologically based (PB) PK models, we propose a parsimonious framework for PK investigation

SUBMITTER: Reali F 

PROVIDER: S-EPMC10794428 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature