Exposure-safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis.

ABSTRACT: Bedaquiline (BDQ) has shown great value in the treatment of multidrug-resistant tuberculosis (MDR-TB) in recent years. However, exposure-safety relationships must be explored to extend the use of BDQ. Two reported safety findings for BDQ are prolongation of the QTc interval and elevation of transaminase levels. In this study, we investigated the potential relationships between BDQ and/or its main metabolite (M2) pharmacokinetic (PK) metrics and QTcF interval or transaminase levels in patients with MDR-TB using the approved dose regimen. Data from 429 patients with MDR-TB from two phase IIb studies were analyzed via nonlinear mixed-effects modeling. Individual model-predicted concentrations and summary PK metrics were evaluated, respectively, in the QTcF interval and transaminase level expo

SUBMITTER: Tanneau L 

PROVIDER: S-EPMC8674006 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature