Polymorphism of the biotransformation gene cytochrome-450 2C9 in patients with tuberculosis

Antonenko, P. B.; Kresyun, V. I.

doi:10.3103/s0891416814030033

Cited by 1 publication

(1 citation statement)

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“…According to the literature data, the main toxicity of isoniazid administration was connected to the formation of toxic metabolites such as acetylhydrazine and hydrazine. [16][17][18] Therefore, the rapid decrease in the isoniazid serum level (in individuals with rapid acetylator phenotype) with the predominant formation of the low-toxicity acetylisoniazid led to a lower risk of isoniazid toxicity. In contrast, the slow decrease in the serum isoniazid concentration (in individuals with slow acetylators) could cause an intensive formation of hydrazine, which explained the higher risk of isoniazid toxicity in this category of individuals.…”

Section: Discussionmentioning

confidence: 99%

Serum isoniazid concentration in the patients as an indicator of the effectiveness and toxicity of tuberculosis treatment

Antonenko

Kresyun

et al. 2019

Pol. Ann. Med.

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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.

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Section: Discussionmentioning

confidence: 99%