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Free Content Steady state pharmacokinetics of cycloserine in patients on terizidone for multidrug-resistant tuberculosis

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SETTING: Terizidone/cycloserine (TRD/CS) is included in standard treatment regimens for multidrug-resistant tuberculosis (MDR-TB) in many countries. The steady state pharmacokinetics (PKs) of CS after TRD administration are not known.

OBJECTIVES AND DESIGN: We recruited in-patients treated with 250–750 mg oral TRD daily as part of standard treatment regimens for pulmonary MDR-TB in Cape Town, South Africa. Plasma CS assays were performed in samples taken pre-dose and at 2, 4, 6, 8 and 10 h post-dose. CS concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. Non-compartmental PK analyses were performed.

RESULTS: Of 35 participants enrolled, 22 were males, and 20 (57%) were infected with the human immunodeficiency virus; the median age was 37 years. The median duration on TRD at the time of sampling was 33 days (interquartile range [IQR] 28–39). The area under the concentration-time curve at 0–10 h (AUC0–10) was 319 μg.h/ml (IQR 267.5–378.7), and peak concentration was 38.1 μg/ml (IQR 32.6–47.2). On multiple regression, dose (mg/kg) was the only factor independently associated with AUC0–10.

CONCLUSION: Steady state concentrations of CS in patients treated with TRD for MDR-TB were higher than those reported with CS formulations. Our findings support once-daily dosing.
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Keywords: HIV; dose duration; dose frequency

Document Type: Research Article

Affiliations: 1: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town 2: Clinical Research Centre, Health Sciences Faculty, University of Cape Town, Cape Town 3: Brooklyn Chest Hospital, Cape Town 4: D P Marais Hospital, Cape Town, South Africa 5: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA

Publication date: January 1, 2018

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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