D A Ivanova, E I Yurovskaya, K Y Galkina, M N Reshetnikov, D V Plotkin, N V Litvinova
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Abstract
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.
期刊介绍：
Терапевтический архив
The journal was founded by the prominent Russian therapists M.P. Konchalovsky and G.F. Lang in 1923. Then its editors-in-chief were Professors V.N. Vinogradov and A.G. Gukasyan. Since 1972, E.I. Chazov, Academician of the Russian Academy of Sciences, has been heading the editorial board of the journal.
Over 90 years, there have been more than 1000 issues where the authors and editorial staff have done their best for readers to keep abreast of current advances in medical science and practice and for physicians to master the advanced principles of recognition and treatment of a wide spectrum of visceral diseases.
The papers published in the journal (editorials, original articles, lectures, reviews, etc.) cover both current scientific achievements and practical experience in diagnosing, treating, and preventing visceral diseases. The authors of publications are not only Russian, but also foreign scientists and physicians. All papers are peer-reviewed by highly qualified Russian specialists.
The journal is published monthly. Traditionally, each issue has predominantly certain thematic areas covering individual therapy specializations. Every year, one of the issues is devoted to related problems in practical medicine (allergology and immunology, neurology and psychiatry, obstetrics, oncology, etc.). This all draws the attention of the reading public to the journal.
The journal is indexed in RSCI (Russian Science Citation Index), PubMed/Medline, Index Medicus, Scopus/EMBASE, Web of Science Core Collection (Science Citation Index Expanded), Web of Science (Russian Science Citation Index - RSCI, Current Contents Connect, BIOSIS Previews), Google Scholar, Ulrich''s Periodicals Directory.
The journal is included in the list of periodicals recommended by the Higher Attestation Committee for publishing the papers containing the basic materials of doctoral and candidate dissertations.
By the decision of the Presidium of the Russian Academy of Medical Sciences, the “Therapevticheskiy Arkhiv” was awarded the Botkin medal. It was admitted to the European Association of Sciences Editors (EASE).
The journal was honored with the Golden Press Fund decoration at the 13th International Press Professional Exhibition.
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