Serum isoniazid concentration in the patients as an indicator of the effectiveness and toxicity of tuberculosis treatment
More details
Hide details
Department of General and Clinical Pharmacology, Odessa National Medical University, Ukraine
Department of Biotechnology and Molecular Biology, Opole University, Poland
Submission date: 2018-09-24
Final revision date: 2018-11-28
Acceptance date: 2018-11-29
Online publication date: 2019-12-11
Corresponding author
Petro B. Antonenko   

Odessa National Medical University, Valichovsky lane, 2, Department of General and Clinical Pharmacology, 65023 Odessa, Ukraine. Tel.: +38 0975875636.
Pol. Ann. Med. 2019;26(2):139-144
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.

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.

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.

The authors declare no conflict of interests.
Dudnyk A, Rzhepishevska O, Rogach K, Kutsyna G, Lange C. Multidrug-resistant tuberculosis in Ukraine at a time of military conflict. Int J Tuberc Lung Dis. 2015;19(4):492–493.
Feshchenko YI, Melnyk VM, Turchenko LV. A fight with tuberculosis in Ukraine: view on a problem. Ukr Pulmonol J. 2016;3:5–10 [in Ukrainian].
Antonenko PB, Kresyun VI, Antonenko КO. [Clusters of Mycobacterium tuberculosis Genotypes in Odesa Region]. Mikrobiol Z. 2016;78(2):103–110 [in Russian].
Winston CA, Peloquin CA, Bradford WZ, et al. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009;48(12):1685–1694.
Um SW, Lee SW, Kwon SY, et al. Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels. Int J Tuberc Lung Dis. 2007;11(9):972–978.
Meloni M, Corti N, Müller D, et al. Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges. Swiss Med Wkly. 2015;145:w14223.
Park JS, Lee JY, Lee YJ, et al. Serum levels of antituberculosis drugs and their effect on tuberculosis treatment outcome. Antimicrobial Agents and Chemotherapy. 2016;60(1):92–98.
Pasipanodya JG, McIlleron H, Burger A, Wash PA, Smith P, Gumbo T. Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J Infect Dis. 2013;208(9):1464–1473.
Ramachandran G, Swaminathan S. Role of pharmacogenomics in the treatment of tuberculosis: a review. Pharmacogenomics Pers Med. 2012;5:89–98.
Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis: an update. Drugs. 2014;74(8):839–854.
Smith P, van Dyk J, Fredericks A. Determination of rifampicin, isoniazid and pyrazinamide by high performance liquid chromatography after their simultaneous extraction from plasma. Int J Tuberc Lung Dis. 1999;3(11 Suppl 3):S325–328.
Ershova OA, Bairova TA, Kolesnikov SI, Kalyuzhnaya OV, Darenskaya MA, Kolesnikova LI. Oxidative stress and catalase gene. Bull Exp Biol Med. 2016;161(3):400–403.
Beutler E. Red Cell Metabolism. A Manual of Biochemical Methods. 3rd Ed. New York: Grune & Stratton; 1984.
Augustynowicz-Kopeć E, Zwolska Z. Bioavailability factors of isoniazid in fast and slow acetylators, healthy volunteers. Acta Pol Pharm. 2002;59(6):452–457.
Gupta VH, Amarapurkar DN, Singh M, et al. Association of N-acetyltransferase 2 and cytochrome P450 2E1 gene polymorphisms with antituberculosis drug-induced hepatotoxicity in Western India. J Gastroenterol Hepatol. 2013;28(8):1368–1374.
Cunningham K, Claus SP, Lindon JC, et al. Pharmacometabonomic characterization of xenobiotic and endogenous metabolic phenotypes that account for inter-individual variation in isoniazid-induced toxicological response. J Proteome Res. 2012;9(11):4630–4642.
Preziosi P. Isoniazid: metabolic aspects and toxicological correlates. Curr Drug Metab. 2007;8(8):839–851.
Antonenko PB, Kresyun VI. [Polymorphism of the biotransformation gene – Cytochrome-450 2C9 in the patients with tuberculosis]. Mol Gen Mikrobiol Virusol. 2014;3:18–22 [in Russian].
Journals System - logo
Scroll to top