farmaecFARMAKOEKONOMIKA. Modern Pharmacoeconomics and PharmacoepidemiologyФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология2070-49092070-4933IRBIS LLC10.17749/2070-4909/farmakoekonomika.2026.360farmaec-1369Research ArticleORIGINAL ARTICLESОРИГИНАЛЬНЫЕ ПУБЛИКАЦИИChemoreactomic analysis of magnesium- and vitamin B6-depleting drugs within the Anatomical Therapeutic Chemical classification as a basis for preventing adverse effects of pharmacotherapyХемореактомный анализ магний- и витамин-B6-выводящих препаратов анатомо-терапевтическо-химической классификации как основа профилактики нежелательных побочных эффектов фармакотерапииhttps://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна, д.м.н., проф. 

WoS ResearcherID: J-4946-2017.

Scopus Author ID: 7003589812. 

ул. Вавилова, д. 44, корп. 2, Москва 119333

Olga A. Gromova, Dr. Sci. Med., Prof.

WoS ResearcherID: J-4946-2017.

Scopus Author ID: 7003589812. 

44 bldg 2 Vavilov Str., Moscow  119333

unesco.gromova@gmail.comhttps://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич, к.ф-м.н., к.х.н. 

WoS ResearcherID: C-7683-2018.

Scopus Author ID: 7003300274. 

ул. Вавилова, д. 44, корп. 2, Москва 119333

Ivan Yu. Torshin, PhD

WoS ResearcherID: C-7683-2018.

Scopus Author ID: 7003300274.

44 bldg 2 Vavilov Str., Moscow  119333

https://orcid.org/0000-0001-6144-5781КалачеваА. Г.KalachevaA. G.

Калачева Алла Геннадьевна, к.м.н., доцент 

Scopus Author ID: 55227267300. 

Шереметевский пр-т, д. 8, Иваново 153012

Alla G. Kalacheva, PhD, Assoc. Prof.

Scopus Author ID: 55227267300. 

8 Sheremetevsky Ave., Ivanovo 153012

https://orcid.org/0009-0007-2744-4268РогозинМ. А.RogozinM. A.

Рогозин Михаил Александрович 

Шереметевский пр-т, д. 8, Иваново 153012

Mikhail A. Rogozin 

8 Sheremetevsky Ave., Ivanovo 153012

Федеральный исследовательский центр «Информатика и управление» Российской академии наукРоссияFederal Research Center “Computer Science and Control”, Russian Academy of SciencesRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Ивановский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияIvanovo State Medical UniversityRussian Federation20232704202600Online First1369Copyright © Gromova O.A., Torshin I.Y., Kalacheva A.G., Rogozin M.A., 20232023Громова О.А., Торшин И.Ю., Калачева А.Г., Рогозин М.А.Gromova O.A., Torshin I.Y., Kalacheva A.G., Rogozin M.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacoeconomics.ru/jour/article/view/1369Background

Background. Many pharmaceuticals, including antibiotics, diuretics, some antitumor agents, hormones, etc., can promote the depletion of magnesium (Mg), pyridoxine (vitamin B6, VB6), and other micronutrients (MNs) in the body. This process may lead to the development of hypomagnesemia and concomitant MN deficiencies, which are associated with a range of adverse effects, including neurotoxicity, cardiotoxicity, hepatotoxicity, etc. Moreover, the resulting micronutrient deficiency (MND) may paradoxically aggravate the underlying pathophysiological mechanisms of the diseases for which these drugs are prescribed, thereby potentially diminishing therapeutic efficacy and contributing to treatment-related complication.

Objective

Objective: Chemoreactomic assessment of anti-micronutrient (anti-MN) effects of all drugs included in the Anatomical Therapeutic Chemical (ATC) classification system.

Material and methods

Material and methods. Using modern data mining techniques, including mathematical approaches from topological data analysis, labeled graph theory (chemographs), and related method, this study performed a systematic computer-based analysis of databases describing the Mg-depleting effects of drugs; original algorithms for numerically predicting the Mg- and VB6-removing effects of drugs. Original algorithms were developed for the numerical prediction of Mg- and VB6-depleting properties of drugs, as well as for the assessment of other anti-MN effects. These algorithms were subsequently applied in a chemoreactomic screening of 2,527 drugs classified within the ATC system.

Results

Results. A database describing anti-MN properties of drugs was created for 24 MN balance indicators for 18 MNs. Algorithms for predicting the anti-MN properties of drugs were developed with a classification accuracy of 92±10% in cross-validation (the accuracy of predicting VB6 MND – 88%, Mg MND – 94-98%). On average, each drug from the ATC group accounts for 8.5±6.5 anti-MN effects. Only 100 out of 2527 (4%) drugs did not exhibit a negative impact on MN, primarily amino acids, MNs themselves, and choline drugs. The most pronounced negative impact of the drugs under study was related to the metabolism of vitamin D3 (505 ATC categories), VB6 (475 ATC categories), iron (419 ATC categories), vitamin B1 (386 ATC categories), and Mg (375 ATC categories). VB6 MND was caused by 1701 drugs, Mg MND – by 1064 drugs. Antibiotics for systemic use (ATC code J01), psycholeptics (N05) and psychoanaleptics (N06), antineoplastic agents (L01), sex hormones and modulators of the reproductive system (G03), analgesics (N02), antidepressants (N06A), diuretics (C03), antihistamines for systemic use (R06A), anti-inflammatory and antirheumatic agents (M01), direct-acting antivirals (J05A), and antiepileptic agents (N03A) were found to affect adversely the homeostasis of both Mg and VB6. A detailed description of the anti-Mg and anti-VB6 properties of these drug classes was provided. The data obtained via chemoreactomic analysis were compared with that obtained by experimental and clinical studies of Mg and VB6 preparations.

Conclusion

Conclusion. The conducted chemoreactomic analysis provides a substantiated basis for supporting pharmacotherapy with selected medicinal preparations based on organic salts of Mg and VB6.

Актуальность

Актуальность. Многие фармацевтические средства (антибиотики, диypeтики, ряд противоопухолевые средства, гормоны и др.) стимулируют потери организмом магния (Mg), пиридоксина (витамина В6, VB6) и других микронутриентов (МН). В результате на фоне возрастающей гипомагнеземии и прочих микронутриентных недостаточностей формируются многочисленные нежелательные побочные эффекты: нейро-, кардио, гепатотоксические и др. Кроме того, из-за формирующейся недостаточной обеспеченности (НДО) МН могут парадоксальным образом усиливаться патофизиологические механизмы, приводящие к заболеванию, при котором использовались соответствующие лекарственные средства (ЛС).

Цель

Цель: хемореактомная оценка антимикронутриентного (анти-МН) действия всех ЛС анатомо-терапевтическо-химической (ATX) классификации.

Материал и методы

Материал и методы. Методами современного интеллектуального анализа данных (математических методов теории топологического анализа данных, теории анализа размеченных графов (хемографов) и др.) последовательно осуществлены систематический компьютерный анализ баз данных по магний-выводящим эффектам ЛС, созданы оригинальные алгоритмы числового прогнозирования Mg- и VB6-выводящего действия ЛС, а также соответствующие алгоритмы для прогнозирования других анти-МН эффектов ЛС и на их основе проведен хемореактомный скрининг 2527 ЛС, представленных в классификаторе ATX.

Результаты

Результаты. Сформирована база данных по анти-МН свойствам ЛС для 24 показателей состояния МН-баланса для 18 МН. Разработаны алгоритмы прогнозирования анти-МН свойств ЛС с аккуратностью классификации 92±10% в кросс-валидации (аккуратность прогнозирования НДО VB6 – 88%, НДО Mg – 94–98%). В среднем на каждое ЛС из ATX приходится 8,5±6,5 анти-МН эффекта, и только 100 из 2527 (4%) ЛС не проявляли негативного воздействия на МН. К последним относились, прежде всего, аминокислоты, собственно МН, холиновые ЛС. Наиболее негативно ЛС влияли на обмен витамина D3 (505 категорий ATX), обмен VB6 (475 категорий ATX), железа (419 категорий ATX), витамина B1 (386 категорий ATX) и Mg (375 категорий ATX). НДО VB6 вызывает 1701 ЛС, НДО Mg – 1064 ЛС. Неблагоприятно на гомеостаз и Mg, и VB6 воздействуют антибиотики для системного применения (код ATX J01), психолептики (N05) и психоаналептики (N06), противоопухолевые средства (L01), половые гормоны и модуляторы половой системы (G03), анальгетики (N02), антидепрессанты (N06A), диypeтики (C03), антигистаминные ЛС для системного применения (R06A), противовоспалительные и противоревматические ЛС (M01), противовирусные ЛС прямого действия (J05A) и противоэпилептические препараты (N03A). Проведено детально описание анти-Mg и анти-VB6 свойств ЛС. Данные, полученные в результате проведения хемореактомного анализа, сопоставлены с данными экспериментальных и клинических исследований препаратов Mg и VB6.

Заключение

Заключение. Результаты хемореактомного анализа позволяют обоснованно сопровождать фармакотерапию теми или иными ЛС препаратами на основе органических солей Mg и VB6.

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The authors declare that there are no conflicts of interest present.