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Free Content Pharmacokinetics of prothionamide in patients with multidrug-resistant tuberculosis

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Abstract:

SETTING: National Masan Tuberculosis Hospital, Masan, South Korea.

OBJECTIVE: To evaluate the pharmacokinetics of prothionamide (PTH) in South Korean patients with multidrug-resistant tuberculosis (MDR-TB) and to investigate whether differences in body mass index (BMI) could explain observed differences in PTH disposition.

DESIGN: Seventeen patients participated in the study; all had MDR-TB and had received combination anti-tuberculosis treatment, including PTH, cycloserine, ofloxacin, para-aminosalicylic acid and streptomycin or kanamycin, for at least 2 weeks. The patients were divided into two groups based on BMI: Group A (18.5 ≤ BMI<23), and Group B (BMI<18.5). Serum samples were collected over 24 h, and the plasma PTH concentration was determined by a validated high-performance liquid chromatography assay.

RESULTS: After steady-state administration of PTH, the mean area under the plasma concentration-time curve from time 0 to 12 h (AUC0–12h) was 11.0 ± 3.7μg h/ml. The mean Tmax and t1/2 were respectively 3.6 h and 2.7 h. No significant difference in PTH disposition was observed between groups A and B, except for ke and t1/2.

CONCLUSION: In the pharmacokinetic parameter estimates for PTH in MDR-TB patients during routine treatment, the pharmacokinetics of PTH did not appear to correlate with extent of emaciation in MDR-TB patients.

Keywords: MDR-TB; pharmacokinetics; prothionamide

Document Type: Regular Paper

Affiliations: 1: Clinical Trial Centre, Kyungpook National University Hospital, Daegu, Korea; and Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, Korea 2: International Tuberculosis Research Centre and National Masan Tuberculosis Hospital, Masan, Korea 3: Clinical Trial Centre, Kyungpook National University Hospital, Daegu, Korea

Publication date: September 1, 2009

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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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