Background: Rifampicin, isoniazid, and pyrazinamide are oral essential anti-tuberculosis drugs on single or combined preparations. Worldwide research has shown that the plasma concentration of anti-tuberculosis drugs with daily therapeutic doses were seen significant lower than permitted in tuberculosis patients, especially for rifampicin and isoniazid. Objective: To investigate plasma concentration of rifampicin, isoniazid, and pyrazinamide in pulmonary tuberculosis and pleural tuberculosis patients. Methods: Determine plasma concentration of rifampicin, isoniazid, and pyrazinamide at 2 hours after administration in 168 tuberculosis patients by the HPLC method. Identify prevalence of low plasma concentrations of anti-tuberculosis drugs. Results: There was a wide range of plasma concentration of rifampicin, isoniazid, and pyrazinamide in the tuberculosis patients. The mean plasma concentration of rifampicin was 6.13 \xb1 4.66 microgram/ml, of isoniazid was 2.99 \xb1 1.94 microgram/ml, pyrazinamide was 38.98 \xb1 18.39 microgram/ml. There was no significant differences in the plasma concentration of rifampicin, isoniazid, and pyrazinamide in groups of pulmonary tuberculosis and pleural tuberculosis patients. Percentage of patients with plasma concentration below therapeutic concentration was 76.83% of rifampicin, 51.85% of isoniazid, 10.13% of pyrazinamide. There were 12.03% of patients who had pyrazinamide concentration higher than the therapeutic range. Conclusions: There was a wide range of plasma concentration in rifampicin, isoniazid, and pyrazinamide of tuberculosis patients. Low plasma concentration of rifampicin and isoniazid are common. It may be necessary to optimize the drug dose by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.
tuberculosis ; rifampicin ; isoniazid ; pyrazinamide

Introduction: Mycobacterium tuberculosis resists rifampicin (RIF) because of mutations in the rpoB (the p subunit of RNA polymerase) gene, mostly in the 81 bp region. \r\n', u'Objectives: Identify the frequency and characteristics relative to drug - resistant rpoB gene mutation in RIF - resistant M. tuberculosis strains. \r\n', u'Subjects and method: 40 M. tuberculosis strains including 11 RIF - sensitive strains and 29 RIF - resistant strains. Some bio molecular techniques were used such as extracting mycobacterial DNA, PCR, cloning, sequencing and analyzing mutation related RIF - resistance on rpoB gene. \r\n', u'Results: No mutation was found on the 81 bp region of rpoB gene of the RIF - sensitive M. tuberculosis strains. The rate of mutation on rpoB gene of 29 RIF - resistant M. tuberculosis strains is 96.6%. We found 12 mutation codon positions on the 81 bp region of the rpoB gene, and the mutation codon positions with high frequency were 531 (51.7%) and 526 (31%). The mutation position found in only one strain is codon 519 (3.4%) but not found in other reports. There are 15 types of drug resistant mutations in which TCG531 TCG is the most common with 50%. Multi - drug resistance was seen in mutable and none mutable cases, with all codon positions and mutable forms. \r\n', u'Conclusion: No mutation was found on the 81 bp region of the rpoB gene of RtF - sensitive M. tuberculosis strains. The rate of mutation on the rpoB gene of RIF - resistant M. tuberculosis strains is 96.6%. The new mutation position found is codon 519. The mutation on the rpoB gene does not determine the multi - drug resistance of M. tuberculosis. \r\n', u'
Mutation ; rpoB gene ; Rifampicin - resistant M. tuberculosis