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