A modeling-based proposal for safe and efficacious reintroduction of bedaquiline after dose interruption: A population pharmacokinetics study.

ABSTRACT: Bedaquiline (BDQ) is recommended for treatment of multidrug-resistant tuberculosis (MDR-TB) for the majority of patients. Given its long terminal half-life and safety concerns, such as QTc-prolongation, re-introducing BDQ after multiple dose interruption is not intuitive and there are currently no existing guidelines. In this simulation-based study, we investigated different loading dose strategies for BDQ re-introduction, taking safety and efficacy into account. Multiple scenarios of time and length of interruption as well as BDQ re-introduction, including no loading dose, 1- and 2-week loading doses (200 mg and 400 mg once daily), were simulated from a previously published population pharmacokinetic (PK) model describing BDQ and its main metabolite M2 PK in patients with MDR-TB. The effi

SUBMITTER: Keutzer L 

PROVIDER: S-EPMC9124352 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature