Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment.

ABSTRACT:

Background

The M2 metabolite of bedaquiline causes QT-interval prolongation, making electrocardiogram (ECG) monitoring of patients receiving bedaquiline for drug-resistant tuberculosis necessary. The objective of this study was to determine the relationship between M2 exposure and Fridericia-corrected QT (QTcF)-interval prolongation and to explore suitable ECG monitoring strategies for 6-month bedaquiline treatment.

Methods

Data from the PROBeX study, a prospective observational cohort study, were used to characterize the relationship between M2 exposure and QTcF. Established nonlinear mixed-effects models were fitted to pharmacokinetic and ECG data. In a virtual patient population, QTcF values were simulated for scenarios with and without concomitant clofazimine. ECG monito

SUBMITTER: van Beek SW 

PROVIDER: S-EPMC9420883 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature