Polymorphism of CYP2E1 genotype is an important criterion for the development of hepatotoxicity before and during TB treatment while increased rifampicin level has no influence on it.
Introduction The low serum concentration of the anti-tuberculosis (TB) drugs in TB patients is observed quite often, but the significance of this phenomenon remains controversial. Aim The aim of the presented research was to clarify the association between isoniazid concentration and TB-treatment outcomes. Material and methods Blood samples were obtained from 86 patients with newly diagnosed pulmonary TB at Odessa Regional TB Hospital in 2015. The level of isoniazid in blood was measured 2 h, 4 h, 6 h, and 24 h after the administration of isoniazid. The medical records of the enrolled patients at the beginning and at the end of the in-patient treatment, and the activity of the biochemical indices were considered. Results and discussion At the end of the in-patient treatment in patients with a serum isoniazid concentration of more than 2 µg/mL (HIC), 4 h after the drug administration, the resorption of TB infiltrates in lungs occurred 1.3 times more frequently than in patients with an isoniazid concentration of less than 2 µg/mL (LIC). According to the culture method, the smear conversion occurred 3.1 times more often in patients with HIC than in the LIC ones. A positive correlation was found between the isoniazid serum level with the bilirubin level, thymol probe, and the AsAT activity, which proved the higher risk of hepatotoxicity in patients with HIC. Conclusions Thus, the measurement of the isoniazid concentration after 4 h of isoniazid administration can predict the outcome of the TB-treatment. It is postulated that the recommended concentration of isoniazid in blood 4 h after its administration > 2 µg/mL.
Bakground: The level of antituberculosis (TB) agents and risk of anti-TB drug-induced liver injury could be predicted by patients' genotype polymorphism of the xenobiotic-metabolizsing enzymes. For example, detection of N-acetyltransferase 2 genotype in TB-patients is very valuable in this relation. Aim: To find the meaning of cyptochrome P-4503A4*1B (CYP3A4*1B) polymorphism in TB-patients. Materials and methods: CYP3A4*1B genotype was detected with the help of polymerase chain reaction among 105 patients with pulmonary TB. The level of rifampicin in the blood was determined spectrophotometrically. We have considered medical records at the beginning and at the end of in-patient treatment. Statistical analysis included Kruskal-Wallis, ANOVA, and Chi-square tests. Results: According to the genotype CYP3A4*1B 91.4% and 8.6% of the patients with pulmonary TB has homozygous wild-type gene (i.e., had high enzymatic activity) -AA and heterozygous AG genotype (moderate enzyme activity), correspondently. The peak of rifampicin's concentration in blood was observed 4 hrs after its intake: 16.25+/-3.92 and 15.03 +/-0.97 mcg/ml in AA and AG genotype correspondently. Thus, there was no significant difference in rifampicin concentration among TB-patients concerning CYP3A4*1B polymorphism. At the beginning of the treatment in TBpatients with AA genotype, the activity of alanine aminotransferase (ALT) and gamma-glutathione transferase (GGT) were on 53.8% and 31.8% higher than in the carriers of AG genotype, however that difference was statistically insignificant regarding to low number of AG genotypes carriers. During treatment in TB hospital in the carriers of AA genotype, the activity of ALT, AST (aspartate aminotransferase), and GGT has enhanced insignificantly, while the activity of ALT, AST, and GGT in AG genotype carriers slightly declined (P>0.05). Moreover, in the end of inpatient treatment, the rate of ALT and GGT in the carriers of AA genotype was on 123.3% (P=0.003; confidential interval = 6.77....29.73) and on 54.8% (P=0.039; confidential interval = 0.73....26.87) correspondently. Conslusion: Polymophism of CYP3A4*1B genotype is an important criterion for the development of hepatotoxicity before and during TB-treatment while it has no influence on rifampicin level in blood.
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