Extrapolation of lung pharmacokinetics of bedaquiline across species using physiologically-based pharmacokinetic modelling.

ABSTRACT:

Aims

Bedaquiline (BDQ) is a first-in-class diarylquinoline (DARQ) and a potent anti-tuberculosis drug, vital in combating multi-drug resistant tuberculosis (TB). Understanding its lung pharmacokinetics (PK) across species is crucial for effective clinical translation. This study aimed to extrapolate BDQ's lung PK from preclinical species to humans, focusing on healthy and TB-infected lung tissue.

Methods

Physiologically-based PK (PBPK) modelling was employed to simulate BDQ's lung distribution in various pulmonary micro-compartments, including cellular lesions and caseous granulomas, using data from mice, rats and dogs. Complex interactions, such as lysosomal trapping within macrophages and anomalous diffusion within the caseum, utilising a catenary model and a time-dependen

SUBMITTER: Karakitsios E 

PROVIDER: S-EPMC12569559 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature