Antonenko P. B.

Effectivness of Pulmonary Tuberculosis Treatment according to Isoniazid Concentration In Blood

About the author:

Antonenko P. B.



Type of article:

Scentific article


Today, tuberculosis (TB) or “white plague” remains a major cause of death among infectious dis-eases in Ukraine. There are a lot of literature data about spreading of sub-effective isoniazid concentration but the meaning of it for tuberculosis course is controversial. That is why the aim of the study was to determine the influence of the concentrations of isoniazid in patients with pulmonary tuberculosis (TB) on the effectiveness of treatment at the outpatient stage. At the beginning of treatment it was performed a measurement of isoniazid concentrations in 84 patients with newly diagnosed TB by Villenberg-Shenderova method by spectrophotometer with the subsequent analysis of medical cards in Odessa regional antituberculosal dispensary in 2012. All TB patients were receiving a standard therapy according to Order of Ministry of Healthcare №384 from 9.06.2006. We have considered medical diagnosis at the beginning and at the end of in-patients treatment including TB-form, characteristics of TB-lesions, bacterial excretion etc. Previously, it was established that the most evident was the difference in content of isoniazid 4 hours after taking the drug. All the patients were divided into two groups with an equal number of patients on the concentration of the drug – 40 patients (47,6%) have had concentration less than 2 mcg/ml (0,48-1,99 mcg/ml), others – 44 patients (52,4%) had concentration over 2 mcg/ml (2,02-6,54 mcg/ml). The duration of in-patient treatment in patients with low concentrations of isoniazid was by 11,2% smaller than in patients with high concentrations of isoniazid (83,0 day against 92,3 days; P=0,024; CI=-17,35. . . 1. 25). Most likely it is connected with the large number of patients with low isoniazid concentration (27. 5%) at the time of evaluation of medical cards were still on treatment and their data were not taken into account, at the same time, all patients with high isoniazid concentration has completed the in-patient treatment (Р<0,05). At the beginning of TB treatment the patients with different concentrations of isoniazid, practically did not differ on details of the tuberculosis process. At the end of in-patient treatment the patients with high concentrations of isoniazid a conversion of destruction was 5,2 times more often, and processes of resorption and petrification were observed in 1,6 times more likely than patients with low concentrations of isoniazid. At the end of in-patient treatment according to bacterioscopy 100% of patients with high isoniazid concentra-tion and 95,1% with low isoniazid concentration were smear-negative. At the time of completion of treatment con-version of smear positive according to culture noted in 3,5 times more frequent in patients with high concentrations of isoniazid than in the group with low concentrations of isoniazid. The duration of bacteriological conversion was not significantly different between the groups and was about 65 days. At the end of in-patient treatment a number of patient with low isoniazid concentration that belong to 4th category (multidrug resistant tuberculosis) was in 2,3 times more than in the group with low concentrations of isoniazid. Thus, determination of the concentrations 4 hours after taking the drug can be recommended to predict the outcome of treatment and possible correction of the therapy of the disease.


tuberculosis, isoniazid, treatment outcome


  • 1. Наказ МОЗ України №384 від 09. 06. 2006 р. «Про затвердження протоколу надання медичної допомоги хворим на туберкульоз»» // Київ, 2006. – 87 с. – (Нормативні директивні правові документи).
  • 2. Раціональний вибір індивідуалізованих режимів хіміотерапії для хворих на мультирезистентний туберкульоз та тубер-кульоз із розширеною резистентністю МБТ до протитуберкульозних препаратів / Н. А. Литвиненко, С. О. Черенько, М. В. Погребна, ю. О. Сенько [та ін.] // Туберкульоз, легеневі хвороби, ВІЛ-інфекція. -2012. – №4(15). – С. 52-57.
  • 3. Резолюція V з’їзду фтизіатрів і пульмонологів України (6–8 листопада 2013 р., м Київ) // Український пуль монологічний журнал. – 2013. – №4. – С. 5-10.
  • 4. Фармакокінетика ізоніазиду у хворих на туберкульоз з різним генотипом ацетилювання / В Й. Кресюн, В. В. Філюк, П. Б. Антоненко, К. К. Рогач [та ін.] // Український пульмонологічний журнал». – 2013. – №3. – С. 24-27.
  • 5. Хіміорезистентний туберкульоз: поширеність та профіль стійкості мікобактерій туберкульозу до антимікобактеріальних препаратів / В. М. Мельник, І. О. Новожилова, В. Г. Матусевич [та ін.] // Український пульмонологічний журнал. – 2013. – №3. – С. 19-23.
  • 6. Шендерова Р. И. Определение активного тубазида в сыворотке крови методом Вилленберга / Р. И. Шендерова // Ла-бораторное дело. – 1975. – №2. – С. 114-116.
  • 7. Clinical characteristics and treatment outcomes of patients with low- and high-concentration isoniazidmonoresistant tuberculosis / Tsai-yu Wang, Shu-Min Lin, Shian-Sen Shie [et al.] // PLOS ONE. – 2014. – Vol. 9, №1. – Р. 1-6.
  • 8. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana / S. Chideya, C. A. Winston, C. A. Peloquin [et al.] // Clin. Infect. Dis. – 2009. – Vol. 48, №12. – P. 1685-1694.
  • 9. Pharmacokinetics and serum concentrations of antimycobacterial drugs in adult Turkish patients / A. Babalık, I. H. Ulus, N. Bakirci [et al.] // Int. J. Tuberc. Lung Dis. – 2013. – Vol. 17, №11. – P. 1442-1447.
  • 10. Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evi-dence for implementation of revised world health organization recommendations / S. Thee, J. A. Seddon, P. R. Donald [et al.] // Antimicrobial agents and chemotherapy. – 2011. – Vol. 55, №12. – P. 5560–5567.
  • 11. Serum drug concentrations predictive of pulmonary tuberculosis outcomes / J. G. Pasipanodya, H. McIlleron, A. Burger, P. A . Wash [et al.] // J. Infect. Dis. – 2013. – Vol. 208, N9. – P. 1464-73.
  • 12. Therapeutic drug monitoring in the treatment of active tuberculosis / A. Babalık, S. Mannix, D. Francis [et al.] // Can. Respir. J. – 2011. – Vol. 18, №4. – P. 225-229.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 2 part 3 (109), 2014 year, 122-126 pages, index UDK [615+577. 21]:616-002. 5:615. 28