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 < or = 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 (AUC(0-12h)) was 11.0 +/- 3.7 microg h/ml. The mean T(max) and t(1/2) 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 t(1/2). 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.
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 < or = 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 (AUC(0-12h)) was 11.0 +/- 3.7 microg h/ml. The mean T(max) and t(1/2) 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 t(1/2). 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.
Authors: Christoph Lange; Ibrahim Abubakar; Jan-Willem C Alffenaar; Graham Bothamley; Jose A Caminero; Anna Cristina C Carvalho; Kwok-Chiu Chang; Luigi Codecasa; Ana Correia; Valeriu Crudu; Peter Davies; Martin Dedicoat; Francis Drobniewski; Raquel Duarte; Cordula Ehlers; Connie Erkens; Delia Goletti; Gunar Günther; Elmira Ibraim; Beate Kampmann; Liga Kuksa; Wiel de Lange; Frank van Leth; Jan van Lunzen; Alberto Matteelli; Dick Menzies; Ignacio Monedero; Elvira Richter; Sabine Rüsch-Gerdes; Andreas Sandgren; Anna Scardigli; Alena Skrahina; Enrico Tortoli; Grigory Volchenkov; Dirk Wagner; Marieke J van der Werf; Bhanu Williams; Wing-Wai Yew; Jean-Pierre Zellweger; Daniela Maria Cirillo Journal: Eur Respir J Date: 2014-03-23 Impact factor: 16.671