Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis.
Monte Carlo simulation
multidrug resistance
pharmacodynamics
population pharmacokinetics
tuberculosis
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
17 06 2021
17 06 2021
Historique:
pubmed:
21
4
2021
medline:
29
6
2021
entrez:
20
4
2021
Statut:
ppublish
Résumé
Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300 mg daily for 3 days, followed by 100 mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (
Identifiants
pubmed: 33875426
pii: AAC.02687-20
doi: 10.1128/AAC.02687-20
pmc: PMC8218646
doi:
Substances chimiques
Clofazimine
D959AE5USF
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0268720Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098316
Pays : United Kingdom
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