Terapevticheskii arkhiv · 2026
[Therapeutic drug monitoring in the treatment of patients with drug-resistant tuberculosis].
Аннотация на английскомСтатьяНазвание и аннотация: Перевод в очереди
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Ivanova D A, Yurovskaya E I, Galkina K Y, Reshetnikov M N, Plotkin D V, Litvinova N V
Аннотация
AIM: Testing of therapeutic drug monitoring in the treatment of drug-resistant tuberculosis.
MATERIALS AND METHODS: We conducted a pilot prospective study including 15 patients with drug-resistant tuberculosis. Serum concentrations of bedaquiline, linezolid, fluoroquinolone, cycloserine, delamanid (C2h) were determined by high-performance liquid chromatography and mass spectrometry. The influence of clinical and pharmacogenetic factors were evaluated.
RESULTS: In most patients, C2h of the drugs were subtherapeutic (57.1% for bedaquiline, 73.3% for linezolid). C2h of bedaquiline were higher in patients with homozygous rs776746 in the CYP3A5 gene (p=0.04), in case of simultaneous omeprazole (p=0.015), high drug load (p=0.005); linezolid - in patients with rs776746 in the CYP3A5 gene (p=0.038) and rs34351236 in the P-glycoprotein gene (p=0.014). The course of chemotherapy was effective in 14 of 15 patients. A factor for cavity closure was a C2h/critical concentration ratio above 1.0 for fluoroquinolone (odds ratio 3.5, 95% confidence interval 1.08-11.24).
CONCLUSION: Therapeutic drug monitoring is a perspective tool for personalized approach to improve treatment outcomes in high-risk drug-resistant tuberculosis patients.
MATERIALS AND METHODS: We conducted a pilot prospective study including 15 patients with drug-resistant tuberculosis. Serum concentrations of bedaquiline, linezolid, fluoroquinolone, cycloserine, delamanid (C2h) were determined by high-performance liquid chromatography and mass spectrometry. The influence of clinical and pharmacogenetic factors were evaluated.
RESULTS: In most patients, C2h of the drugs were subtherapeutic (57.1% for bedaquiline, 73.3% for linezolid). C2h of bedaquiline were higher in patients with homozygous rs776746 in the CYP3A5 gene (p=0.04), in case of simultaneous omeprazole (p=0.015), high drug load (p=0.005); linezolid - in patients with rs776746 in the CYP3A5 gene (p=0.038) and rs34351236 in the P-glycoprotein gene (p=0.014). The course of chemotherapy was effective in 14 of 15 patients. A factor for cavity closure was a C2h/critical concentration ratio above 1.0 for fluoroquinolone (odds ratio 3.5, 95% confidence interval 1.08-11.24).
CONCLUSION: Therapeutic drug monitoring is a perspective tool for personalized approach to improve treatment outcomes in high-risk drug-resistant tuberculosis patients.