Detection of serum isoniazid concentration in patients with multidrug-resistant tuberculosis using high-performance liquid chromatography

To study Mycobacterium tuberculosis (MTB) genotypes circulating in the Sakha Republic (Yakutia), molecular genetic analysis of multidrug-resistant MTB was performed using real-time PCR-test. The study showed predominance of Beijing genotype with resistance to isoniazid caused by mutations in kat G gene alone (86.2 %), in both kat G and inh A genes (10.3 %), or in inh A alone (3,5 %). In this work, we studied variations in serum isoniazid concentration in patients with multidrug-resistant tuberculosis, using different routes of drug administration: regional lymphotropic, intravenous infusion (IV), intramuscular injection (IM), and oral. Blood samples were obtained 1.5, 6, and 9 hours after administration of the drug. Levels and variations of isoniazid serum concentrations were assessed at intervals, using high-performance liquid chromatography (HPLC). For assessing the efficiency of treatment, patients were divided to four groups according to isoniazid administration routes. The study established that serum isoniazid concentrations observed with regional lymphotropic administration, were initially the lowest (4.2 mg/L), compared to IV infusion, IM, and oral administration routes (8,12.5, and 17.1 mg/L, respectively), but showed slower reduction of concentration. It was also noticed, that after 9 hours, the serum concentration of isoniazid was reliably higher in regional lymphotropicgroup, than in the rest of study groups (2.2 vs. 0.8 mg/L). Higher therapeutic effect of intralymphatic drug administration could be explained by the formation within the regional lymphatic network of a localized area around the site of injection containing enhanced concentration of isoniazid and allowing extended drug release into bloodstream, resulting further in prolonged drug biotransformation.

mycobacterium tuberculosis, genotype, isoniazid, drug administration routes, high pressure liquid chromatography

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