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Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis

Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis

International Journal of Tuberculosis and Lung Disease 23(1): 99-104

Bedaquiline (BDQ) has been approved for the treatment of multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB). For many patients treatment is prolonged beyond the recommended 6 months. The long-term pharmacokinetics of BDQ have yet to be elucidated. To evaluate plasma concentrations of BDQ during treatment and its elimination after treatment discontinuation. This was a retrospective study conducted in two units in France that provide treatment for MDR/XDR-TB. Sociodemographic, clinical, biological and therapeutic parameters were collected from patients currently or formerly treated with BDQ. Plasma concentrations of BDQ and its active M2 (N-desmethyl) metabolite were determined using ultra-performance liquid chromatography with tandem mass spectrometry. Thirteen patients were recruited (35 samples): 10 (31 samples) during BDQ treatment and 3 (4 samples) after BDQ discontinuation. The median duration of treatment with BDQ was 11 months (interquartile range [IQR] 8-14). During treatment, the median plasma BDQ concentrations and M2 were respectively 1264 ng/ml (IQR 910-2244) and 252 ng/ml (IQR 134-290). In one patient, BDQ was detected in the plasma 200 days after treatment discontinuation (528 ng/ml). BDQ and M2 plasma concentrations were consistent with good drug efficacy/safety profiles, suggesting good treatment adherence with no relevant drug interactions. The long-term plasma detectability of BDQ after treatment discontinuation may raise the spectre of the emergence of resistance.

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Accession: 066116947

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PMID: 30674381

DOI: 10.5588/ijtld.18.0042

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