Association between effectiveness of tuberculosis treatment and cytochrome P-4502E1 polymorphism of the patients

Antonenko, P. B.; Butov, Dmytro; Kresyun, V. I.; Antonenko, Kateryna; Butova, Tetyana

doi:10.4103/ijmy.ijmy_168_17

Cited by 9 publications

(5 citation statements)

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“…This could be explained by a higher serum concentration of rifampicin and slightly higher serum concentration of isoniazid in patients with *AA genotype, compared to the group of *AG genotype carriers. At the same time, according to previous studies, according to the CYP3A4*1G genotype, in "slow metabolizers" (mutant homozygous genotype), the risk of developing of hepatotoxicity during anti-tuberculosis therapy exceeded the similar indicator of "rapid metabolizers" [9].…”

Section: клінічна практикаmentioning

confidence: 72%

“…For example, TB patients with "slow metabolizers" (SM) genotype of CYP2C9 gene had the highest serum isoniazid and rifampicin level and the most favorable treatment outcome comparatively to "rapid metabolizers" (RM) genotype group [8]. According to CYP3A4*1B genotype in TB patients with RM genotype, the indexes of cytolysis (alanine aminotransferase, aspartate aminotransferase and bile stasis (gamma-glutathione transferase) were higher comparatively to SM genotype both before and after in-patient treatment [9]. According to the literature, the enzyme cytochrome (CYP) 3A4/5 is involved in the metabolism of more than a one-third of all drugs [10].…”

Section: клінічна практикаmentioning

confidence: 99%

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Prognostic Value of Cyp3a4*1b Polymorphism in Patients With Pulmonary Tuberculosis

Poludenko,

Antonenko,

Antonenko

et al. 2024

The Odesa Medical Journal

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Introduction. Previously it was found that in slow metabolizers according to CYP3A4*1G genotype after completion of in-patient stage of anti-tuberculosis treatment, the level of cytolysis and toxicity indexes was much higher than in rapid metabolizers. The aim of the present research was to find the meaning of CYP3A4*1В polymorphism in tuberculosis (TB) patients for the level of isoniazid and rifampicin as well as for the outcome and toxicity development during in-patient TB treatment.Materials and methods. The medical records of 105 patients with pulmonary tuberculosis were examined. All these patients had primary pulmonary tuberculosis. They were receiving in-patient treatment at the Odesa Regional Center for Socially Significant Diseases (previouslythe Odesa Regional Tuberculosis Dispensary) in 2012-2014. The study was conducted under the Declaration of Helsinki standards.Results. After in-patient treatment, the activity of cytolysis markers as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the cholestasis marker as gamma-glutathione transferase (GGT) in TB-patients with *AA genotype increased insignificantly by 7.0%, 9.3%, and 4.5% (p>0.05); in patients with the *AG genotype, the activity of ALT, AST and GGT, on the contrary, had a tendency for decreasing -by 18.7%, 3.0% and 9.0% (p>0.05); a similar trend was observed concerning the number of patients with increased activity of ALT, AST and GGT. At the end of treatment, the average activity of ALT in carriers of the *AA genotype was 1.8 times higher than in carriers of the *AG genotype (p=0.046; . Conclusion.At the beginning of anti-tuberculosis chemotherapy, it is recommended to determine the CYP3A4*1B genotype in patients with pulmonary tuberculosis, which allow identifying the groups of patients with the *AG genotype, which is characterized by a greater risk of developing sub-therapeutic rifampicin concentrations in the blood during treatment and prove the usefulness of personalized choice of rifampicin dosage according to the CYP3A4*1B genotype.

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Section: клінічна практикаmentioning

confidence: 72%

Section: клінічна практикаmentioning

confidence: 99%

Prognostic Value of Cyp3a4*1b Polymorphism in Patients With Pulmonary Tuberculosis

Poludenko,

Antonenko,

Antonenko

et al. 2024

The Odesa Medical Journal

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“…CYP2E1 also increased in mPxr −/− mice treated with both rifampicin and isoniazid (1.47-relative change). Polymorphisms associated with increased CYP2E1 activity in humans increase the incidence of drug-induced liver injury (DILI) [ 42 , 43 , 44 ]. Inhibiting CYP2E1 is protective against isoniazid-induced hepatotoxicity in mice [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Toxicoproteomic Profiling of hPXR Transgenic Mice Treated with Rifampicin and Isoniazid

Brewer

Kodali

et al. 2020

Cells

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Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure. Recent reports have characterized the nature of hPXR-mediated hepatotoxicity and the systemic toxicity of antitubercular drugs. The antitubercular drug isoniazid plays a role in such pathologic states as acute intermittent porphyria, anemia, hepatotoxicity, hypercoagulable states (deep vein thrombosis, pulmonary embolism, or ischemic stroke), pellagra (vitamin B3 deficiency), peripheral neuropathy, and vitamin B6 deficiency. However, the mechanisms by which isoniazid administration leads to these states are unclear. To elucidate the mechanism of rifampicin- and isoniazid-induced liver and systemic injury, we performed tandem mass tag mass spectrometry-based proteomic screening of mPxr–/– and hPXR mice treated with combinations of rifampicin and isoniazid. Proteomic profiling analysis suggested that the hPXR liver proteome is affected by antitubercular therapy to disrupt [Fe–S] cluster assembly machinery, [2Fe–2S] cluster-containing proteins, cytochrome P450 enzymes, heme biosynthesis, homocysteine catabolism, oxidative stress responses, vitamin B3 metabolism, and vitamin B6 metabolism. These novel findings provide insight into the etiology of some of these processes and potential targets for subsequent investigations. Data are available via ProteomeXchange with identifier PXD019505.

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“…Intravenous chemotherapy increases the concentration of ATD in the blood in a short period of time, ensures a rapid access of these drugs to the focus of tuberculous inflammation and the use of solutions of intravenous ATD provides faster detoxication in patients with TB [15,22]. In addition, the results of studies during the past years have proved that the antimicrobial effect of ATD depends only on their maximum concentration in the blood, whereas the duration of contact with MBT is not significant [10,25]. We demonstrated that intravenous administration of ATD allows creating a high level of bacteriostatic blood activity and maximum concentration in blood serum of patients as much as 2.5 times higher compared to oral use.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis

Butova¹,

Бутов²

2021

Int J Mycobacteriol

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Introduction:The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis (pulmonary TB). Material and methods:The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 and 68. All patients with newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in the study. The patients were allocated to two groups. The first (control) group of 46 patients received standard chemotherapy orally. The second (main) group consisted of 46 patients who were prescribed isoniazid, rifampin, ethambutol by i.v. infusion, and pyrazinamide orally as a part of the standard treatment. Results: Symptoms of intoxication and chest manifestations in pulmonary TB patients from the second group were eliminated faster than the same symptoms in the group 1. In the group 2, the mycobacterial clearance in sputum smears was achieved more rapidly, and up to 2 months it was reached in 37 patients (80.43%), while in the control group in 25 patients (54.35%),p = 0.0066. Destruction healing and inflitrative change alleviation after 4 months was reached in 38 patients (82.61%) (in control group -28 (60.87%), (p = 0.0192). No additional negative effects were detected when compared with the control group at any time. Conclusions: Thanks to i.v. chemotherapy, clinical manifestations of the in-patients with pulmonary TB were eliminated faster, severe side effects of anti-TB drugs were not noticed, time of bacterial clearance and healing of destruction was shorter, healing frequency of destructions increased and the of residual changes decreased.

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Association between effectiveness of tuberculosis treatment and cytochrome P-4502E1 polymorphism of the patients

Abstract: 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.

Cited by 9 publications

References 1 publication

Prognostic Value of Cyp3a4*1b Polymorphism in Patients With Pulmonary Tuberculosis

Prognostic Value of Cyp3a4*1b Polymorphism in Patients With Pulmonary Tuberculosis

Toxicoproteomic Profiling of hPXR Transgenic Mice Treated with Rifampicin and Isoniazid

Efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis

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