Pharmacokinetics of prothionamide in patients with multidrug-resistant tuberculosis
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.
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: 2009-09-01
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