Pharmacokinetics of prothionamide in patients with multidrug-resistant tuberculosis.
METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Lee
H W
HW
Clinical Trial Centre, Kyungpook National University Hospital, Daegu, Korea; Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
Kim
D W
DW
Park
J H
JH
Kim
S-D
SD
Lim
M-S
MS
Phapale
P B
PB
Kim
E-H
EH
Park
S K
SK
Yoon
Y-R
YR
D000284:Administration, Oral; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015992:Body Mass Index; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D004614:Emaciation / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011515:Prothionamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D056910:Republic of Korea; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D055815:Young Adult
D000995:Antitubercular Agents; D011515:Prothionamide