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Home / The International Journal of Tuberculosis and Lung Disease, Volume 22, Number 1

Pharmacokinetic interaction between bedaquiline and clofazimine in patients with drug-resistant tuberculosis

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BACKGROUND: Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ.

METHODS: We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB. This was a secondary analysis of a study designed to explore drug-drug interactions between BDQ and antiretrovirals.

RESULTS: Of 46 participants, 30 were on concomitant CFZ when intensive PK sampling of BDQ was done. CFZ did not have a statistically significant effect on BDQ bioavailability (−9.1%, 90%CI −22.8 to +7.1; P = 0.19) or on BDQ and M2 clearance (+12.2%, 90%CI −13.7 to +38; P = 0.32).

CONCLUSION: We did not find a statistically significant PK drug-drug interaction between BDQ and CFZ, but cannot exclude a potentially clinically relevant interaction due to the wide confidence intervals of the estimated interaction effects.

Keywords: BDQ; CFZ; TB; drug-drug interaction; population pharmacokinetics

Document Type: Research Article

Affiliations: 1: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa 2: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden 3: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden, Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands

Publication date: 01 January 2018

This article was made available online on 16 November 2017 as a Fast Track article with title: "Pharmacokinetic interaction between bedaquiline and clofazimine in patients with drug-resistant tuberculosis".

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

    The IJTLD is dedicated to understanding lung disease and to the dissemination of knowledge leading to better lung health. To allow us to share scientific research as rapidly as possible, the IJTLD is fast-tracking the publication of certain articles as preprints prior to their publication. Read fast-track articles.

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