Predictions of Bedaquiline Central Nervous System Exposure in Patients with Tuberculosis Meningitis Using Physiologically based Pharmacokinetic Modeling.
Krina MehtaPavel BalazkiPiet H van der GraafTingjie GuoJ G Coen van HasseltPublished in: Clinical pharmacokinetics (2024)
The whole-body PBPK model for bedaquiline and M2 predicted unbound concentrations in brain to be significantly lower than the unbound concentrations in the lung at clinically relevant doses. Our findings suggest that bedaquiline may result in relatively inferior efficacy against drug-resistant TBM when compared with efficacy against drug-resistant pulmonary TB.
Keyphrases
- drug resistant
- multidrug resistant
- acinetobacter baumannii
- mycobacterium tuberculosis
- cerebrospinal fluid
- pulmonary hypertension
- white matter
- resting state
- emergency department
- hiv aids
- pseudomonas aeruginosa
- brain injury
- hiv infected
- cystic fibrosis
- functional connectivity
- subarachnoid hemorrhage
- cerebral ischemia