epilepsiaEpilepsy and paroxysmal conditionsЭпилепсия и пароксизмальные состояния2077-83332311-4088IRBIS LLC10.17749/2077-8333/epi.par.con.2026.274epilepsia-1352Research ArticleSCIENTIFIC SURVEYSНАУЧНЫЕ ОБЗОРЫPharmacogenomics and pharmacometabolomics of levetiracetam in personalized neurotoxicity risk assessmentФармакогеномика и фармакометаболомика леветирацетама в персонализированной оценке риска нейротоксичности.https://orcid.org/0000-0002-2840-837XШнайдерН. А.ShnayderN. A.

Шнайдер Наталья Алексеевна, д.м.н., проф. 

WoS ResearcherID: M-7084-2014. Scopus Author ID: 24503222300

ул. Бехтерева, д. 3, Санкт-Петербург 192019

ул. Партизана Железняка, д. 1, Красноярск 660022

Natalia A. Shnayder, Dr. Sci. Med., Prof. 

WoS ResearcherID: M-7084-2014. Scopus Author ID: 24503222300

3 Bekhterev Str., Saint Petersburg 192019

1 Partizan Zheleznyak Str., Krasnoyarsk 660022

naschnaider@yandex.ruhttps://orcid.org/0000-0001-8279-4198БадерВ. В.BaderV. V.

Бадер Виолетта Владимировна 

Scopus Author ID: 58076147700

ул. Бехтерева, д. 3, Санкт-Петербург 192019

Violetta V. Bader 

Scopus Author ID: 58076147700

3 Bekhterev Str., Saint Petersburg 192019

https://orcid.org/0009-0005-5895-1778ПекарецН. А.PekaretsN. A.

Пекарец Николай Александрович 

ул. Красного Восстания, д. 1, Иркутск 664003

Nikolai A. Pekarets 

1 Krasnogo Vosstaniya Str., Irkutsk 664003

https://orcid.org/0000-0002-7836-5179БыковЮ. Н.BykovYu. A.

Быков Юрий Николаевич, д.м.н., проф. 

WoS ResearcherID: S-6938-2016. Scopus Author ID: 57200671414

ул. Красного Восстания, д. 1, Иркутск 664003

Yury N. Bykov, Dr. Sci. Med., Prof. 

WoS ResearcherID: S-6938-2016. Scopus Author ID: 57200671414

1 Krasnogo Vosstaniya Str., Irkutsk 664003

https://orcid.org/0009-0004-6045-3906ШируковаА. М.ShirukovaA. M.

Ширукова Асият Мухтаровна 

ул. Бехтерева, д. 3, Санкт-Петербург 192019

Asiyat M. Shirukova 

3 Bekhterev Str., Saint Petersburg 192019

https://orcid.org/0000-0003-1874-9434НасыроваР. Ф.NasyrovaR. F.

Насырова Регина Фаритовна, д.м.н.

WoS ResearcherID: H-7787-2016

ул. Бехтерева, д. 3, Санкт-Петербург 192019

ул. Александра Матросова, д. 22, Санкт-Петербург 194100

Regina F. Nasyrova, Dr. Sci. Med. 

WoS ResearcherID: H-7787-2016

3 Bekhterev Str., Saint Petersburg 192019

22 Alexander Matrosov Str., Saint-Petersburg 194100

Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской ФедерацииРоссияBekhterev National Medical Research Centre for Psychiatry and Neurology; Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской ФедерацииРоссияBekhterev National Medical Research Centre for Psychiatry and NeurologyRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Иркутский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияIrkutsk State Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный педиатрический медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияBekhterev National Medical Research Centre for Psychiatry and Neurology; Saint Petersburg State Pediatric Medical UniversityRussian Federation202603082026182158–172Copyright © Shnayder N.A., Bader V.V., Pekarets N.A., Bykov Y.A., Shirukova A.M., Nasyrova R.F., 20262026Шнайдер Н.А., Бадер В.В., Пекарец Н.А., Быков Ю.Н., Ширукова А.М., Насырова Р.Ф.Shnayder N.A., Bader V.V., Pekarets N.A., Bykov Y.A., Shirukova A.M., Nasyrova R.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epilepsia.su/jour/article/view/1352

Levetiracetam (LEV) is one of the most commonly prescribed second-generation antiepileptic drugs due to its selective binding to the synaptic vesicle protein SV2A, predictable pharmacokinetics, minimal drug interactions, and low teratogenic risk. The clinical spectrum of LEV includes focal seizures (as monotherapy or adjunct), and tonic-clonic seizures. Despite its “pharmacokinetic simplicity”, LEV exhibits marked interindividual variability in efficacy and tolerability, primarily due to behavioral and neuropsychiatric adverse drug reactions (ADRs). Less commonly, immune-inflammatory skin, hematologic, hepatic ADRs, and case reports of myotoxic and viscerotoxic reactions occur. The development of LEV-induced ADRs is partially determined by genetic factors (targets/transporters/esterases, vulnerability of monoaminergic networks) and metabolomic shifts (tryptophan-kynurenine pathway, lipid and redox changes), which justifies the application of “omics” approaches for personalized LEV therapy. The review on domestic and international studies (from 2015 to 2025) in the field of LEV-related pharmacogenomics and pharmacometabolomics is presented, aimed at identifying genetic and metabolic biomarkers associated with the risk of neurotoxicity. It demonstrated, that data on SV2A gene and neurotransmitter genes polymorphisms and neurotransmitter genes are still inconsistent. LEV is metabolized by extrahepatic esterases to a pharmacologically inactive compound (L057); no clinically significant reactive LEV metabolites have been identified. The most reproducible pharmacogenetic biomarkers are polymorphisms in the ABCB1 (efflux across the blood-brain barrier) and CES1 (rate of hydrolysis) genes. Pharmacometabolomics confirms the usefulness of assessing the LEV/L057 ratio as an exposure metabolic biomarker. Changes in the tryptophan-kynurenine pathway are primarily experimental, while lipidomic/redox findings are heterogeneous and lack stable clinical validation. Clinically, the risk of neurotoxic behavioral ADRs may be associated with variability in exposure and individual neurobiological vulnerability of neurons to LEV. Personalization of LEV therapy relies on selective therapeutic drug monitoring, assessment of renal function / pregnancy / augmented renal clearance, and modelinformed dosing. However, routine “omics” testing in real clinical practice has not been developed. LEV has a favorable pharmacokinetic profile without the formation of reactive metabolites. The clinical heterogeneity of therapeutic response and ADRs are mainly accounted for by pharmacodynamic and immune-inflammatory mechanisms also involving transporter proteins and esterases. Integration of pharmacogenomics (ABCB1, CES1), targeted pharmacometabolomics (LEV/L057, kynurenine pathway biomarkers), “selective” therapeutic drug monitoring, and model-informed LEV dosing may improve the safety and efficacy of LEV use, creating a realistic framework for personalized epileptology.

Леветирацетам (ЛЕВ) – один из наиболее часто назначаемых противоэпилептических препаратов второй генерации благодаря селективному связыванию с белком синаптических везикул SV2A, предсказуемой фармакокинетике, минимальным межлекарственным взаимодействиям и низкому тератогенному риску. Клинический спектр ЛЕВ включает фокальные приступы (монотерапия/адъювант) и тонико-клонические приступы. При всей «фармакокинетической простоте» ЛЕВ характеризуется выраженной межиндивидуальной вариабельностью эффективности и переносимости, прежде всего за счет поведенческих/нейропсихиатрических нежелательных реакций (НР). Реже наблюдаются иммуновоспалительные кожные, гематологические, печеночные и казуистические миотоксические и висцеротоксические НР. Развитие ЛЕВ-индуцированных НР частично детерминировано генетическими факторами (белок-мишень/ транспортеры/эстеразы, уязвимость моноаминергических сетей) и фармакометаболомными сдвигами (триптофанкинурениновая ось, липидом/редокс), что обосновывает применение «омикс»-подходов для персонализации терапии ЛЕВ. Представлен обзор отечественных и зарубежных исследований (c 2015 по 2025 гг.) в области фармакогеномики и фармакометаболомики ЛЕВ, направленных на поиск генетических и метаболических биомаркеров, ассоциированных с риском ЛЕВ-индуцированной нейротоксичности. Продемонстрировано, что данные фармакогенетических исследований полиморфизмов гена SV2A и генов нейромедиаторных систем пока неоднородны. ЛЕВ метаболизируется внепеченочными эстеразами до фармакологически неактивного соединения (L057), но клинически значимых реактивных метаболитов ЛЕВ не выявлено. Наиболее воспроизводимыми фармакогенетическими биомаркерами являются полиморфизмы гена ABCB1 (эффлюкс ЛЕВ через гематоэнцефалический барьер) и гена CES1 (скорость гидролиза ЛЕВ). Фармакометаболомика подтверждает полезность оценки соотношения ЛЕВ/L057 как экспозиционного метаболического биомаркера ЛЕВ-индуцированной нейротоксичности. Изменения в триптофан-кинурениновой оси преимущественно экспериментальные, а липидомные/редокс-находки гетерогенны и не имеют устойчивой клинической валидации. Клинически риск нейротоксических поведенческих НР может быть связан с вариабельностью экспозиции и индивидуальной нейробиологической уязвимостью нейронов к ЛЕВ. Персонализация терапии ЛЕВ опирается на избирательный терапевтический лекарственный мониторинг, оценке почечной функции / беременности и модель-информированное дозирование. Однако рутинное «омикс»-тестирование в реальной клинической практике пока не разработано. ЛЕВ обладает благоприятным фармакокинетическим профилем без образования реактивных метаболитов. Клиническая гетерогенность терапевтического ответа и НР обусловлены преимущественно фармакодинамическими и иммуновоспалительными механизмами с вкладом белков-транспортеров и эстераз. Интеграция фармакогеномики (ABCB1, CES1), таргетной фармакометаболомики (ЛЕВ/L057, биомаркеров кинурениновой оси), «селективного» терапевтического лекарственного мониторинга и модель-информированного дозирования ЛЕВ может повысить безопасность и эффективность применения ЛЕВ, создавая реалистичный контур персонализированной эпилептологии.

леветирацетамметаболизмфармакогеномикафармакометаболомикатерапевтический лекарственный мониторингфармакогенетическое тестированиенейротоксичностьбиомаркербезопасностьнежелательная лекарственная реакцияперсонализированная медицинаlevetiracetammetabolismpharmacogomicspharmacometabolomicstherapeutic drug monitoringpharmacogenetic testingneurotoxicitybiomarkersafetyadverse drug reactionpersonalized medicineReferencesLevetiracetam (UCB-L059). Available at: https://www.selleckchem.com/products/Levetiracetam.html#:~:text=Levetiracetam%20(UCB%2DL059%2C%20SIB,dependent%20calcium%20(Ca2+)%20channel (accessed 10.11.2025).Levetiracetam (UCB-L059). Available at: https://www.selleckchem.com/products/Levetiracetam.html#:~:text=Levetiracetam%20(UCB%2DL059%2C%20SIB,dependent%20calcium%20(Ca2+)%20channel (accessed 10.11.2025).Ковалёв И.Г., Васильева Е.В., Боков Р.О. и др. Изучение эффектов леветирацетама и нового производного 4-фенилпирролидона ГИЖ-290 в закрытом крестообразном лабиринте у мышей линий BALB/c и C57BL/6. Фармакокинетика и фармакодинамика. 2017; 2: 25–9.Kovalev I.G., Vasileva E.V., Bokov R.O., et al. The effects of levetiracetam and a new 4-phenylpyrrolidone derivative GIZh-290 in a closed cross-maze in BALB/c and C57BL / 6 mice. Pharmacokinetics and Pharmacodynamics. 2017; 2: 25–9 (in Russ.).Kumar A., Maini K., Kadian R. Levetiracetam. Treasure Island (FL): StatPearls Publishing; 2025. Available at: https://www.ncbi.nlm.nih.gov/books/NBK499890 (accessed 10.11.2025)Kumar A., Maini K., Kadian R. Levetiracetam. Treasure Island (FL): StatPearls Publishing; 2025. Available at: https://www.ncbi.nlm.nih.gov/books/NBK499890 (accessed 10.11.2025)Contreras-García I.J., Cárdenas-Rodríguez N., Romo-Mancillas A., et al. Levetiracetam mechanisms of action: from molecules to systems. Pharmaceuticals. 2022; 15 (4): 475. https://doi.org/10.3390/ph15040475.Contreras-García I.J., Cárdenas-Rodríguez N., Romo-Mancillas A., et al. Levetiracetam mechanisms of action: from molecules to systems. Pharmaceuticals. 2022; 15 (4): 475. https://doi.org/10.3390/ph15040475.Klitgaard H., Matagne A., Nicolas J.M., et al. Brivaracetam: rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016; 57 (4): 38–48. https://doi.org/10.1111/epi.13340.Klitgaard H., Matagne A., Nicolas J.M., et al. Brivaracetam: rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016; 57 (4): 38–48. https://doi.org/10.1111/epi.13340.Panebianco M., Bresnahan R., Marson A.G. Lamotrigine add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2023; 12 (12): CD001909. https://doi.org/10.1002/14651858.CD001909.pub4.Panebianco M., Bresnahan R., Marson A.G. Lamotrigine add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2023; 12 (12): CD001909. https://doi.org/10.1002/14651858.CD001909.pub4.Государственный реестр лекарственных средств. Леветирацетам. URL: https://grls.pharm-portal.ru/grls/8d1dab4c-ed82-4aa2-86cad852494f6f07#summary (дата обращения 11.11.2025).State Register of Medicines. Levetiracetam. Available at: https://grls.pharm-portal.ru/grls/8d1dab4c-ed82-4aa2-86cad852494f6f07#summary (in Russ.) (accessed 11.11.2025).Najafi S., Alavi M.S., Sadeghnia H.R. A meta-analytic evaluation of the efficacy and safety of levetiracetam for treating myoclonic seizures. Heliyon. 2025; 11 (3): e42244. https://doi.org/10.1016/j.heliyon.2025.e42244.Najafi S., Alavi M.S., Sadeghnia H.R. A meta-analytic evaluation of the efficacy and safety of levetiracetam for treating myoclonic seizures. Heliyon. 2025; 11 (3): e42244. https://doi.org/10.1016/j.heliyon.2025.e42244.Verrotti A., Cerminara C., Coppola G., et al. Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Dev Med Child Neurol. 2008; 50 (1): 29–32. https://doi.org/10.1111/j.1469-8749.2007.02009.x.Verrotti A., Cerminara C., Coppola G., et al. Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Dev Med Child Neurol. 2008; 50 (1): 29–32. https://doi.org/10.1111/j.1469-8749.2007.02009.x.Castro C.A, Nascimento F.A., Beltran-Corbellini Á., et al. Levetiracetam, from broad-spectrum use to precision prescription: a narrative review and expert opinion. Seizure. 2023; 107: 121–31. https://doi.org/10.1016/j.seizure.2023.03.017.Castro C.A, Nascimento F.A., Beltran-Corbellini Á., et al. Levetiracetam, from broad-spectrum use to precision prescription: a narrative review and expert opinion. Seizure. 2023; 107: 121–31. https://doi.org/10.1016/j.seizure.2023.03.017.Lippa C.F., Rosso A., Hepler M., et al. Levetiracetam: a practical option for seizure management in elderly patients with cognitive impairment. Am J Alzheimers Dis Other Demen. 2010; 25 (2): 149–54. https://doi.org/10.1177/1533317508325095.Lippa C.F., Rosso A., Hepler M., et al. Levetiracetam: a practical option for seizure management in elderly patients with cognitive impairment. Am J Alzheimers Dis Other Demen. 2010; 25 (2): 149–54. https://doi.org/10.1177/1533317508325095.Nevitt S.J., Sudell M., Cividini S., et al. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2022; 4 (4): CD011412. https://doi.org/10.1002/14651858.Nevitt S.J., Sudell M., Cividini S., et al. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2022; 4 (4): CD011412. https://doi.org/10.1002/14651858.Methaneethorn J., Leelakanok N. Population pharmacokinetics of levetiracetam: a systematic review. Curr Rev Clin Exp Pharmacol. 2022; 17 (2): 122–34. https://doi.org/10.2174/1574884716666210223110658.Methaneethorn J., Leelakanok N. Population pharmacokinetics of levetiracetam: a systematic review. Curr Rev Clin Exp Pharmacol. 2022; 17 (2): 122–34. https://doi.org/10.2174/1574884716666210223110658.Levetiracetam. Available at: https://go.drugbank.com/drugs/DB01202 (accessed 15.11.2025).Levetiracetam. Available at: https://go.drugbank.com/drugs/DB01202 (accessed 15.11.2025).Asconapé J.J. Use of antiepileptic drugs in hepatic and renal disease. Handb Clin Neurol. 2014; 119: 417–32. https://doi.org/10.1016/B978-07020-4086-3.00027-8.Asconapé J.J. Use of antiepileptic drugs in hepatic and renal disease. Handb Clin Neurol. 2014; 119: 417–32. https://doi.org/10.1016/B978-07020-4086-3.00027-8.Shi M., Liu C., He L., et al. Therapeutic drug monitoring and the therapeutic reference range of levetiracetam for Chinese patients: problems and issues. Seizure. 2023; 109: 26–33. https://doi.org/10.1016/j.seizure.2023.05.010.Shi M., Liu C., He L., et al. Therapeutic drug monitoring and the therapeutic reference range of levetiracetam for Chinese patients: problems and issues. Seizure. 2023; 109: 26–33. https://doi.org/10.1016/j.seizure.2023.05.010.Bodor G.S., Rands A.J. Quantitative LC-MS/MS method for the simultaneous measurement of six antiepileptics and pentobarbital in human serum. Methods Mol Biol. 2024; 2737: 43–54. https://doi.org/10.1007/978-1-0716-3541-4_5.Bodor G.S., Rands A.J. Quantitative LC-MS/MS method for the simultaneous measurement of six antiepileptics and pentobarbital in human serum. Methods Mol Biol. 2024; 2737: 43–54. https://doi.org/10.1007/978-1-0716-3541-4_5.Feng S., Bridgewater B., Strickland E.C., McIntire G. A rapid LC-MS-MS method for the quantitation of antiepileptic drugs in urine. J Anal Toxicol. 2020; 44 (7): 688–96. https://doi.org/10.1093/jat/bkaa095.Feng S., Bridgewater B., Strickland E.C., McIntire G. A rapid LC-MS-MS method for the quantitation of antiepileptic drugs in urine. J Anal Toxicol. 2020; 44 (7): 688–96. https://doi.org/10.1093/jat/bkaa095.Li W., Yang X., Chen Q., et al. Monitoring levetiracetam concentration in saliva during pregnancy is stable and feasible. CNS Neurosci Ther. 2024; 30 (7): e14827. https://doi.org/10.1111/cns.14827.Li W., Yang X., Chen Q., et al. Monitoring levetiracetam concentration in saliva during pregnancy is stable and feasible. CNS Neurosci Ther. 2024; 30 (7): e14827. https://doi.org/10.1111/cns.14827.Patsalos P.N., Spencer E.P., Berry D.J. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018; 40 (5): 526–48. https://doi.org/10.1097/FTD.0000000000000546.Patsalos P.N., Spencer E.P., Berry D.J. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018; 40 (5): 526–48. https://doi.org/10.1097/FTD.0000000000000546.Choong E., Vassallo P., Aícua-Rapún I., et al. Clinical value of saliva therapeutic drug monitoring of newer antiseizure medications. Seizure. 2025; 125: 106–12. https://doi.org/10.1016/j.seizure.2025.01.013.Choong E., Vassallo P., Aícua-Rapún I., et al. Clinical value of saliva therapeutic drug monitoring of newer antiseizure medications. Seizure. 2025; 125: 106–12. https://doi.org/10.1016/j.seizure.2025.01.013.Jacob S., Nair A.B. An updated overview on therapeutic drug monitoring of recent antiepileptic drugs. Drugs R D. 2016; 16 (4): 303– 16. https://doi.org/10.1007/s40268-016-0148-6.Jacob S., Nair A.B. An updated overview on therapeutic drug monitoring of recent antiepileptic drugs. Drugs R D. 2016; 16 (4): 303– 16. https://doi.org/10.1007/s40268-016-0148-6.Dwivedi R., Singh M., Kaleekal T., et al. Concentration of antiepileptic drugs in persons with epilepsy: a comparative study in serum and saliva. Int J Neurosci. 2016; 126 (11): 972–8. https://doi.org/10.3109/00207454.2015.1088848.Dwivedi R., Singh M., Kaleekal T., et al. Concentration of antiepileptic drugs in persons with epilepsy: a comparative study in serum and saliva. Int J Neurosci. 2016; 126 (11): 972–8. https://doi.org/10.3109/00207454.2015.1088848.Jenjirattithigarn N., Worachat N., Horsuwan S., et al. Determination of plasma levetiracetam level by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and its application in pharmacokinetics studies in neonates. J Chromatogr B Analyt Technol Biomed Life Sci. 2018; 1085: 13–20. https://doi.org/10.1016/j.jchromb.2018.03.037.Jenjirattithigarn N., Worachat N., Horsuwan S., et al. Determination of plasma levetiracetam level by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and its application in pharmacokinetics studies in neonates. J Chromatogr B Analyt Technol Biomed Life Sci. 2018; 1085: 13–20. https://doi.org/10.1016/j.jchromb.2018.03.037.Zhang M., Jin Y., Li W., et al. Quantitation of levetiracetam concentrations in plasma and saliva samples by ultra-performance liquid chromatography-tandem mass spectrometry: application to therapeutic drug monitoring for pregnant women with epilepsy. Biomed Chromatogr. 2024; 38 (2): e5777. https://doi.org/10.1002/bmc.5777.Zhang M., Jin Y., Li W., et al. Quantitation of levetiracetam concentrations in plasma and saliva samples by ultra-performance liquid chromatography-tandem mass spectrometry: application to therapeutic drug monitoring for pregnant women with epilepsy. Biomed Chromatogr. 2024; 38 (2): e5777. https://doi.org/10.1002/bmc.5777.Jarvie D., Mahmoud S.H. Therapeutic drug monitoring of levetiracetam in select populations. J Pharm Pharm Sci. 2018; 21 (1s): 149s–76s. https://doi.org/10.18433/jpps30081.Jarvie D., Mahmoud S.H. Therapeutic drug monitoring of levetiracetam in select populations. J Pharm Pharm Sci. 2018; 21 (1s): 149s–76s. https://doi.org/10.18433/jpps30081.WHO Model Lists of Essential Medicines. Available at: https://www.who.int/groups/expert-committee-on-selection-and-use-of-essentialmedicines/essential-medicines-lists (accessed 22.11.2025).WHO Model Lists of Essential Medicines. Available at: https://www.who.int/groups/expert-committee-on-selection-and-use-of-essentialmedicines/essential-medicines-lists (accessed 22.11.2025).Приложение № 1 к распоряжению Правительства Российской Федерации от 12 октября 2019 г. № 2406-р. URL: https://docs.cntd.ru/document/563469457?marker=6540IN (дата обращения 22.11.2025).Appendix No. 1 to the Order of the Government of the Russian Federation dated October 12, 2019 No. 2406-r. Available at: https://docs.cntd.ru/document/563469457?marker=6540IN (in Russ.) (accessed 22.11.2025).Kasimova A., Labutin D., Gvozdetsky A., Bozhkova S. Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty. Chin J Traumatol. 2024; 27 (1): 27–33. https://doi.org/10.1016/j.cjtee.2023.06.003.Kasimova A., Labutin D., Gvozdetsky A., Bozhkova S. Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty. Chin J Traumatol. 2024; 27 (1): 27–33. https://doi.org/10.1016/j.cjtee.2023.06.003.Zhao T., Yu J., Wang T.T., et al. Impact of ABCB1 polymorphism on levetiracetam serum concentrations in epileptic Uygur children in China. Ther Drug Monit. 2020; 42 (6): 886–92. https://doi.org/10.1097/FTD.0000000000000805.Zhao T., Yu J., Wang T.T., et al. Impact of ABCB1 polymorphism on levetiracetam serum concentrations in epileptic Uygur children in China. Ther Drug Monit. 2020; 42 (6): 886–92. https://doi.org/10.1097/FTD.0000000000000805.Grewal G.K., Kukal S., Kanojia N., еt al. In vitro assessment of the effect of antiepileptic drugs on expression and function of ABC transporters and their interactions with ABCC2. Molecules. 2017; 22 (10): 1484. https://doi.org/10.3390/molecules22101484.Grewal G.K., Kukal S., Kanojia N., еt al. In vitro assessment of the effect of antiepileptic drugs on expression and function of ABC transporters and their interactions with ABCC2. Molecules. 2017; 22 (10): 1484. https://doi.org/10.3390/molecules22101484.Шнайдер Н.А., Бадер В.В., Насырова Р.Ф., Киссин М.Я. Мультиомические технологии в прогнозировании нейротоксичности ламотриджина: современные возможности (обзор). Безопасность и риск фармакотерапии. 2026; 14 (1): 51–65. https://doi.org/10.30895/2312-7821-2025-498.Shnayder N.A., Bader V.V., Nasyrova R.F., Kissin M.Ya. Multi-omics in predicting lamotrigine neurotoxicity: current opportunities (review). Safety and Risk of Pharmacotherapy. 2026; 14 (1): 51–65 (in Russ.). https://doi.org/10.30895/2312-7821-2025-498.Nowack A., Malarkey E.B., Yao J., et al. Levetiracetam reverses synaptic deficits produced by overexpression of SV2A. PLoS One. 2011; 6 (12): e29560. https://doi.org/10.1371/journal.pone.0029560.Nowack A., Malarkey E.B., Yao J., et al. Levetiracetam reverses synaptic deficits produced by overexpression of SV2A. PLoS One. 2011; 6 (12): e29560. https://doi.org/10.1371/journal.pone.0029560.Contreras-García I.J., Gómez-Lira G., Phillips-Farfán B.V., et al. Synaptic vesicle protein 2A expression in glutamatergic terminals is associated with the response to levetiracetam treatment. Brain Sci. 2021; 11 (5): 531. https://doi.org/10.3390/brainsci11050531.Contreras-García I.J., Gómez-Lira G., Phillips-Farfán B.V., et al. Synaptic vesicle protein 2A expression in glutamatergic terminals is associated with the response to levetiracetam treatment. Brain Sci. 2021; 11 (5): 531. https://doi.org/10.3390/brainsci11050531.Sanz-Blasco S., Piña-Crespo J.C., Zhang X., et al. Levetiracetam inhibits oligomeric Aβ-induced glutamate release from human astrocytes. Neuroreport. 2016; 27 (9): 705–9. https://doi.org/10.1097/WNR.0000000000000601.Sanz-Blasco S., Piña-Crespo J.C., Zhang X., et al. Levetiracetam inhibits oligomeric Aβ-induced glutamate release from human astrocytes. Neuroreport. 2016; 27 (9): 705–9. https://doi.org/10.1097/WNR.0000000000000601.Rainesalo S., Keränen T., Palmio J., et al. Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004; 29 (1): 319–24. https://doi.org/10.1023/b:nere.0000010461.34920.0c.Rainesalo S., Keränen T., Palmio J., et al. Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004; 29 (1): 319–24. https://doi.org/10.1023/b:nere.0000010461.34920.0c.Nagarkatti N., Deshpande L.S., DeLorenzo R.J. Levetiracetam inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture. Neurosci Lett. 2008; 436 (3): 289–93. https://doi.org/10.1016/j.neulet.2008.02.076.Nagarkatti N., Deshpande L.S., DeLorenzo R.J. Levetiracetam inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture. Neurosci Lett. 2008; 436 (3): 289–93. https://doi.org/10.1016/j.neulet.2008.02.076.Dubovsky S.L., Daurignac E., Leonard K.E., Serotte J.C. Levetiracetam, calcium antagonism, and bipolar disorder. J Clin Psychopharmacol. 2015; 35 (4): 422–7. https://doi.org/10.1097/JCP.0000000000000343.Dubovsky S.L., Daurignac E., Leonard K.E., Serotte J.C. Levetiracetam, calcium antagonism, and bipolar disorder. J Clin Psychopharmacol. 2015; 35 (4): 422–7. https://doi.org/10.1097/JCP.0000000000000343.Viguier T., Agier M.S., Jonville-Béra A.P., et al. Drug clustering to anticipate new aspects of drug safety profile: application to gabapentinoids and other voltage-gated calcium channel ligand drugs. Br J Clin Pharmacol. 2024; 90 (2): 475–82. https://doi.org/10.1111/bcp.15931.Viguier T., Agier M.S., Jonville-Béra A.P., et al. Drug clustering to anticipate new aspects of drug safety profile: application to gabapentinoids and other voltage-gated calcium channel ligand drugs. Br J Clin Pharmacol. 2024; 90 (2): 475–82. https://doi.org/10.1111/bcp.15931.Deshpande L.S., Delorenzo R.J. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy. Front Neurol. 2014; 5: 11. https://doi.org/10.3389/fneur.2014.00011.Deshpande L.S., Delorenzo R.J. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy. Front Neurol. 2014; 5: 11. https://doi.org/10.3389/fneur.2014.00011.Alhowail A.H., Alharbi A.M. Exploring how levetiracetam mitigates toxicity and ameliorates memory impairment. Front Pharmacol. 2025; 16: 1651414. https://doi.org/10.3389/fphar.2025.1651414.Alhowail A.H., Alharbi A.M. Exploring how levetiracetam mitigates toxicity and ameliorates memory impairment. Front Pharmacol. 2025; 16: 1651414. https://doi.org/10.3389/fphar.2025.1651414.Italiano D., Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update. Clin Pharmacokinet. 2013; 52 (8): 627–45. https://doi.org/10.1007/s40262013-0067-4.Italiano D., Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update. Clin Pharmacokinet. 2013; 52 (8): 627–45. https://doi.org/10.1007/s40262013-0067-4.Arfman I.J., Wammes-van Der Heijden E.A., ter Horst P.G.J., et al. Therapeutic drug monitoring of antiepileptic drugs in women with epilepsy before, during, and after pregnancy. Clin Pharmacokinet. 2020; 59 (4): 427–45. https://doi.org/10.1007/s40262-019-00845-2.Arfman I.J., Wammes-van Der Heijden E.A., ter Horst P.G.J., et al. Therapeutic drug monitoring of antiepileptic drugs in women with epilepsy before, during, and after pregnancy. Clin Pharmacokinet. 2020; 59 (4): 427–45. https://doi.org/10.1007/s40262-019-00845-2.Sourbron J., Chan H., Wammes-van D.H.E., et al. Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure. 2018; 62: 131–5. https://doi.org/10.1016/j.seizure.2018.09.004.Sourbron J., Chan H., Wammes-van D.H.E., et al. Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure. 2018; 62: 131–5. https://doi.org/10.1016/j.seizure.2018.09.004.Kharouba M., Aboelezz A., Kung J.Y., Mahmoud S.H. The impact of augmented renal clearance on the pharmacokinetics of levetiracetam in critically ill patients: a literature review. J Clin Pharmacol. 2025; 65 (7): 815–34. https://doi.org/10.1002/jcph.70007.Kharouba M., Aboelezz A., Kung J.Y., Mahmoud S.H. The impact of augmented renal clearance on the pharmacokinetics of levetiracetam in critically ill patients: a literature review. J Clin Pharmacol. 2025; 65 (7): 815–34. https://doi.org/10.1002/jcph.70007.Bilbao-Meseguer I., Barrasa H., Rodríguez-Gascón A., et al. Optimization of levetiracetam dosing regimen in critically ill patients with augmented renal clearance: a Monte Carlo simulation study. J Intensive Care. 2022; 10 (1): 21. https://doi.org/0.1186/s40560-02200611-w.Bilbao-Meseguer I., Barrasa H., Rodríguez-Gascón A., et al. Optimization of levetiracetam dosing regimen in critically ill patients with augmented renal clearance: a Monte Carlo simulation study. J Intensive Care. 2022; 10 (1): 21. https://doi.org/0.1186/s40560-02200611-w.Ong C.L.J., Goh P.S.J., Teo M.M., et al. Pharmacokinetics of levetiracetam in neurosurgical ICU patients. J Crit Care. 2021; 64: 255– 61. https://doi.org/10.1016/j.jcrc.2021.04.013.Ong C.L.J., Goh P.S.J., Teo M.M., et al. Pharmacokinetics of levetiracetam in neurosurgical ICU patients. J Crit Care. 2021; 64: 255– 61. https://doi.org/10.1016/j.jcrc.2021.04.013.Cook A.M., Hall K., Kolpek J.H., et al. Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance. BMC Neurol. 2024; 24 (1): 12. https://doi.org/10.1186/s12883-023-03515-w.Cook A.M., Hall K., Kolpek J.H., et al. Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance. BMC Neurol. 2024; 24 (1): 12. https://doi.org/10.1186/s12883-023-03515-w.Badura-Stronka M., Kuszel Ł., Wencel-Warot A., et al. Broadening the phenotypic spectrum of the presumably epilepsy-related SV2A gene variants. Epilepsy Res. 2023; 190: 107101. https://doi.org/10.1016/j.eplepsyres.2023.107101.Badura-Stronka M., Kuszel Ł., Wencel-Warot A., et al. Broadening the phenotypic spectrum of the presumably epilepsy-related SV2A gene variants. Epilepsy Res. 2023; 190: 107101. https://doi.org/10.1016/j.eplepsyres.2023.107101.Wang D., Zhou Q., Ren L., et al. Levetiracetam-induced a new seizure type in a girl with a novel SV2A gene mutation. Clin Neurol Neurosurg. 2019; 181: 64–6. https://doi.org/10.1016/j.clineuro.2019.03.020.Wang D., Zhou Q., Ren L., et al. Levetiracetam-induced a new seizure type in a girl with a novel SV2A gene mutation. Clin Neurol Neurosurg. 2019; 181: 64–6. https://doi.org/10.1016/j.clineuro.2019.03.020.Serajee F.J., Huq A.M. Homozygous mutation in synaptic vesicle glycoprotein 2A gene results in intractable epilepsy, involuntary movements, microcephaly, and developmental and growth retardation. Pediatr Neurol. 2015; 52 (6): 642–51. https://doi.org/10.1016/j.pediatrneurol.2015.02.011.Serajee F.J., Huq A.M. Homozygous mutation in synaptic vesicle glycoprotein 2A gene results in intractable epilepsy, involuntary movements, microcephaly, and developmental and growth retardation. Pediatr Neurol. 2015; 52 (6): 642–51. https://doi.org/10.1016/j.pediatrneurol.2015.02.011.Shi J., Anderson D., Lynch B.A., et al. Combining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding. Biochem Soc Trans. 2011; 39 (5): 1341–7. https://doi.org/10.1042/BST0391341.Shi J., Anderson D., Lynch B.A., et al. Combining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding. Biochem Soc Trans. 2011; 39 (5): 1341–7. https://doi.org/10.1042/BST0391341.Lee J., Daniels V., Sands Z.A., et al. Exploring the interaction of SV2A with racetams using homology modelling, molecular dynamics and site-directed mutagenesis. PLoS One. 2015; 10 (2): e0116589. https://doi.org/10.1371/journal.pone.0116589.Lee J., Daniels V., Sands Z.A., et al. Exploring the interaction of SV2A with racetams using homology modelling, molecular dynamics and site-directed mutagenesis. PLoS One. 2015; 10 (2): e0116589. https://doi.org/10.1371/journal.pone.0116589.Tokudome K., Okumura T., Terada R., et al. A missense mutation of the gene encoding synaptic vesicle glycoprotein 2A (SV2A) confers seizure susceptibility by disrupting amygdalar synaptic GABA release. Front Pharmacol. 2016; 7: 210. https://doi.org/10.3389/fphar.2016.00210.Tokudome K., Okumura T., Terada R., et al. A missense mutation of the gene encoding synaptic vesicle glycoprotein 2A (SV2A) confers seizure susceptibility by disrupting amygdalar synaptic GABA release. Front Pharmacol. 2016; 7: 210. https://doi.org/10.3389/fphar.2016.00210.Ohno Y., Tokudome K. Therapeutic role of synaptic vesicle glycoprotein 2A (SV2A) in modulating epileptogenesis. CNS Neurol Disord Drug Targets. 2017; 16 (4): 463–71. https://doi.org/10.2174/18715273166661 70404115027.Ohno Y., Tokudome K. Therapeutic role of synaptic vesicle glycoprotein 2A (SV2A) in modulating epileptogenesis. CNS Neurol Disord Drug Targets. 2017; 16 (4): 463–71. https://doi.org/10.2174/18715273166661 70404115027.Carunchio I., Pieri M., Ciotti M.T., et al. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia. 2007; 48 (4): 654–62. https://doi.org/10.1111/j.1528-1167.2006.00973.x.Carunchio I., Pieri M., Ciotti M.T., et al. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia. 2007; 48 (4): 654–62. https://doi.org/10.1111/j.1528-1167.2006.00973.x.Hughes S., Blumenthal M., Johnson A., et al. Pharmacokinetics and pharmacodynamics of levetiracetam in neonatal seizures: what we still need to know. J Pediatr Pharmacol Ther. 2025; 30 (2): 170–81. https://doi.org/10.5863/1551-6776-30.2.170.Hughes S., Blumenthal M., Johnson A., et al. Pharmacokinetics and pharmacodynamics of levetiracetam in neonatal seizures: what we still need to know. J Pediatr Pharmacol Ther. 2025; 30 (2): 170–81. https://doi.org/10.5863/1551-6776-30.2.170.Magadmi R. Pharmacogenetics of anti-seizure medications in Arab countries: a comprehensive review. Future Sci OA. 2025; 11 (1): 2528490. https://doi.org/10.1080/20565623.2025.2528490.Magadmi R. Pharmacogenetics of anti-seizure medications in Arab countries: a comprehensive review. Future Sci OA. 2025; 11 (1): 2528490. https://doi.org/10.1080/20565623.2025.2528490.Yu L., Liao W.P., Yi Y.H., et al. ABCB1 G2677T/A polymorphism is associated with the risk of drug-resistant epilepsy in Asians. Epilepsy Res. 2015; 115: 100–8. https://doi.org/0.1016/j.eplepsyres.2015.05.015.Yu L., Liao W.P., Yi Y.H., et al. ABCB1 G2677T/A polymorphism is associated with the risk of drug-resistant epilepsy in Asians. Epilepsy Res. 2015; 115: 100–8. https://doi.org/0.1016/j.eplepsyres.2015.05.015.Li H., Wang B., Chang C., et al. The roles of variants in human multidrug resistance (MDR1) gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies. PLoS One. 2015; 10 (3): e0122043. https://doi.org/10.1371/journal.pone.0122043.Li H., Wang B., Chang C., et al. The roles of variants in human multidrug resistance (MDR1) gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies. PLoS One. 2015; 10 (3): e0122043. https://doi.org/10.1371/journal.pone.0122043.Stasiołek M., Romanowicz H., Połatyńska K., et al. Association between C3435T polymorphism of MDR1 gene and the incidence of drugresistant epilepsy in the population of Polish children. Behav Brain Funct. 2016; 12 (1): 21. https://doi.org/10.1186/s12993-016-0106-z.Stasiołek M., Romanowicz H., Połatyńska K., et al. Association between C3435T polymorphism of MDR1 gene and the incidence of drugresistant epilepsy in the population of Polish children. Behav Brain Funct. 2016; 12 (1): 21. https://doi.org/10.1186/s12993-016-0106-z.Chouchi M., Kaabachi W., Klaa H., et al. Relationship between ABCB1 3435TT genotype and antiepileptic drugs resistance in epilepsy: updated systematic review and meta-analysis. BMC Neurol. 2017; 17 (1): 32. https://doi.org/10.1186/s12883-017-0801-x.Chouchi M., Kaabachi W., Klaa H., et al. Relationship between ABCB1 3435TT genotype and antiepileptic drugs resistance in epilepsy: updated systematic review and meta-analysis. BMC Neurol. 2017; 17 (1): 32. https://doi.org/10.1186/s12883-017-0801-x.Chouchi M., Klaa H., Ben-Youssef Turki I., Hila L. ABCB1 polymorphisms and drug-resistant epilepsy in a Tunisian population. Dis Markers. 2019; 2019: 1343650. https://doi.org/10.1155/2019/1343650.Chouchi M., Klaa H., Ben-Youssef Turki I., Hila L. ABCB1 polymorphisms and drug-resistant epilepsy in a Tunisian population. Dis Markers. 2019; 2019: 1343650. https://doi.org/10.1155/2019/1343650.Усольцева А.А., Кривцова Е.Р., Дмитренко Д.В. Фармакокинетические факторы развития поведенческих нежелательных реакций на фоне приема противоэпилептических препаратов (клинический случай). Вестник Северо-Восточного федерального университета им. М.К. Аммосова. Серия: Медицинские науки. 2024; 3: 58–65.Usoltseva A.A., Krivcova E.R., Dmitrenko D.V. Pharmacogenetic factors in the development of behavioral adverse reactions while taking antiepileptic drugs: a clinical case. Vestnik of North-Eastern Federal University. Medical Sciences. 2024; 3: 58–65 (in Russ.).Kikuyama H., Hanaoka T., Kanazawa T., et al. The mechanism of anti-epileptogenesis by levetiracetam treatment is similar to the spontaneous recovery of idiopathic generalized epilepsy during adolescence. Psychiatry Investig. 2017; 14 (6): 844–50. https://doi.org/10.4306/pi.2017.14.6.844.Kikuyama H., Hanaoka T., Kanazawa T., et al. The mechanism of anti-epileptogenesis by levetiracetam treatment is similar to the spontaneous recovery of idiopathic generalized epilepsy during adolescence. Psychiatry Investig. 2017; 14 (6): 844–50. https://doi.org/10.4306/pi.2017.14.6.844.McGonigal A., Becker C., Fath J., et al. BDNF as potential biomarker of epilepsy severity and psychiatric comorbidity: pitfalls in the clinical population. Epilepsy Res. 2023; 195: 107200. https://doi.org/10.1016/j.eplepsyres.2023.107200.McGonigal A., Becker C., Fath J., et al. BDNF as potential biomarker of epilepsy severity and psychiatric comorbidity: pitfalls in the clinical population. Epilepsy Res. 2023; 195: 107200. https://doi.org/10.1016/j.eplepsyres.2023.107200.Cardile V., Pavone A., Gulino R., et al. Expression of brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) in rat astrocyte cultures treated with levetiracetam. Brain Res. 2003; 976 (2): 227–33. https://doi.org/10.1016/s0006-8993(03)02720-3.Cardile V., Pavone A., Gulino R., et al. Expression of brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) in rat astrocyte cultures treated with levetiracetam. Brain Res. 2003; 976 (2): 227–33. https://doi.org/10.1016/s0006-8993(03)02720-3.Warburton A., Miyajima F., Shazadi K., et al. NRSF and BDNF polymorphisms as biomarkers of cognitive dysfunction in adults with newly diagnosed epilepsy. Epilepsy Behav. 2016; 54: 117–27. https://doi.org/10.1016/j.yebeh.2015.Warburton A., Miyajima F., Shazadi K., et al. NRSF and BDNF polymorphisms as biomarkers of cognitive dysfunction in adults with newly diagnosed epilepsy. Epilepsy Behav. 2016; 54: 117–27. https://doi.org/10.1016/j.yebeh.2015.Campbell C., McCormack M., Patel S., et al. A pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam. Epilepsia. 2022; 63 (6): 1563–70. https://doi.org/10.1111/epi.17228.2026Campbell C., McCormack M., Patel S., et al. A pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam. Epilepsia. 2022; 63 (6): 1563–70. https://doi.org/10.1111/epi.17228.2026Иващенко Д.В., Хоанг С.З., Тазагулова М.Х. и др. Полиморфные варианты DRD2 rs1800497 и ABCB1 3435C>T ассоциированы с параметрами безопасности антипсихотиков у подростков с острым психотическим эпизодом: результаты пилотного исследования. Неврология, нейропсихиатрия, психосоматика. 2020; 12 (5): 24–31. https://doi.org/10.14412/2074-2711-2020-5-24-31.Ivashchenko D.V., Khoang S.Z., Tazagulova M.K., et al. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T are associated with antipsychotic safety parameters in adolescents with an acute psychotic episode: the results of a pilot study. Nevrologiya, neiropsikhiatriya, psikhosomatika / Neurology, Neuropsychiatry, Psychosomatics. 2020; 12 (5): 24–31 (in Russ.). https://doi.org/10.14412/2074-2711-2020-5-24-31.Усольцева А.А., Дмитренко Д.В., Зобова С.Н. и др. Генетические факторы риска развития поведенческих нежелательных реакций у пациентов с эпилепсией, принимающих леветирацетам. Неврология, нейропсихиатрия, психосоматика. 2019; 11 (4): 68–76. https://doi.org/10.14412/2074-2711-2019-4-68-76.Usoltseva A.A., Dmitrenko D.V., Zobova S.N., et al. Genetic risk factors for behavioral adverse reactions in epileptic patients taking levetiracetam. Nevrologiya, neiropsikhiatriya, psikhosomatika / Neurology, Neuropsychiatry, Psychosomatics. 2019; 11 (4): 68–76 (in Russ.). https://doi.org/10.14412/2074-2711-2019-4-68-76.Josephson C.B., Engbers J.D.T., Jette N., et al. Prediction tools for psychiatric adverse effects after levetiracetam prescription. JAMA Neurol. 2019; 76 (4): 440–6. https://doi.org/10.1001/jamaneurol.2018.4561.Josephson C.B., Engbers J.D.T., Jette N., et al. Prediction tools for psychiatric adverse effects after levetiracetam prescription. JAMA Neurol. 2019; 76 (4): 440–6. https://doi.org/10.1001/jamaneurol.2018.4561.Patsalos P.N., Ghattaura S., Ratnaraj N., Sander J.W. In situ metabolism of levetiracetam in blood of patients with epilepsy. Epilepsia. 2006; 47 (11): 1818–21. https://doi.org/10.1111/j.1528-1167.2006.00819.x.Patsalos P.N., Ghattaura S., Ratnaraj N., Sander J.W. In situ metabolism of levetiracetam in blood of patients with epilepsy. Epilepsia. 2006; 47 (11): 1818–21. https://doi.org/10.1111/j.1528-1167.2006.00819.x.Peng Y., Fu S., Liu H., Lucia L.A. Accurately determining esterase activity via the isosbestic point of p-nitrophenol. BioRes. 2016; 11 (4): 10099–111. https://doi.org/10.15376/biores.11.4.10099-10111.Peng Y., Fu S., Liu H., Lucia L.A. Accurately determining esterase activity via the isosbestic point of p-nitrophenol. BioRes. 2016; 11 (4): 10099–111. https://doi.org/10.15376/biores.11.4.10099-10111.Fukuyama K., Okada M. Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites. Br J Pharmacol. 2018; 175 (22): 4253–65. https://doi.org/10.1111/bph.14491.Fukuyama K., Okada M. Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites. Br J Pharmacol. 2018; 175 (22): 4253–65. https://doi.org/10.1111/bph.14491.Lee C.Y., Chen C.C., Liou H.H. Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. Br J Pharmacol. 2009; 158 (7): 1753–62. https://doi.org/10.1111/j.1476-5381.2009.00463.x.Lee C.Y., Chen C.C., Liou H.H. Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. Br J Pharmacol. 2009; 158 (7): 1753–62. https://doi.org/10.1111/j.1476-5381.2009.00463.x.Yu Y., Sun F.J. Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy. Ibrain. 2024; 11 (1): 44–58. https://doi.org/10.1002/ibra.12162.Yu Y., Sun F.J. Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy. Ibrain. 2024; 11 (1): 44–58. https://doi.org/10.1002/ibra.12162.Giorgini F., Huang S.Y., Sathyasaikumar K.V., et al. Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. J Biol Chem. 2013; 288 (51): 36554–66. https://doi.org/10.1074/jbc.M113.503813.Giorgini F., Huang S.Y., Sathyasaikumar K.V., et al. Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. J Biol Chem. 2013; 288 (51): 36554–66. https://doi.org/10.1074/jbc.M113.503813.Cuartero M.I., de la Parra J., García-Culebras A., et al. The kynurenine pathway in the acute and chronic phases of cerebral ischemia. Curr Pharm Des. 2016; 22 (8): 1060–73. https://doi.org/10.2174/1381612822666151214125950.Cuartero M.I., de la Parra J., García-Culebras A., et al. The kynurenine pathway in the acute and chronic phases of cerebral ischemia. Curr Pharm Des. 2016; 22 (8): 1060–73. https://doi.org/10.2174/1381612822666151214125950.Miller A.H., Raison C.L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016; 16 (1): 22–34. https://doi.org/10.1038/nri.2015.5.Miller A.H., Raison C.L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016; 16 (1): 22–34. https://doi.org/10.1038/nri.2015.5.Yang T.W., Moon J., Kim T.J., et al. HLA-A*11:01 is associated with levetiracetam-induced psychiatric adverse events. PLoS One. 2018; 13 (7): e0200812. https://doi.org/10.1371/journal.pone.0200812.Yang T.W., Moon J., Kim T.J., et al. HLA-A*11:01 is associated with levetiracetam-induced psychiatric adverse events. PLoS One. 2018; 13 (7): e0200812. https://doi.org/10.1371/journal.pone.0200812.Bansal R., Suri V., Chopra S., et al. Levetiracetam use during pregnancy in women with epilepsy: preliminary observations from a tertiary care center in Northern India. Indian J Pharmacol. 2018; 50 (1): 39–43. https://doi.org/10.4103/ijp.IJP_692_17.Bansal R., Suri V., Chopra S., et al. Levetiracetam use during pregnancy in women with epilepsy: preliminary observations from a tertiary care center in Northern India. Indian J Pharmacol. 2018; 50 (1): 39–43. https://doi.org/10.4103/ijp.IJP_692_17.Anti-seizure medications & pregnancy suitability. Available at: https:// epilepsypregnancy.com/for-clinicians/anti-seizure-medications (accessed 03.12.2025).Anti-seizure medications & pregnancy suitability. Available at: https:// epilepsypregnancy.com/for-clinicians/anti-seizure-medications (accessed 03.12.2025).Fallik N., Trakhtenbroit I., Fahoum F., Goldstein L. Therapeutic drug monitoring in pregnancy: levetiracetam. Epilepsia. 2024; 65 (5): 1285– 93. https://doi.org/10.1111/epi.17925.Fallik N., Trakhtenbroit I., Fahoum F., Goldstein L. Therapeutic drug monitoring in pregnancy: levetiracetam. Epilepsia. 2024; 65 (5): 1285– 93. https://doi.org/10.1111/epi.17925.Anti-seizure medication level checks during pregnancy. Available at: https://epilepsypregnancy.com/for-clinicians/anti-seizure-medicationslevel-checks (accessed 03.12.2025).Anti-seizure medication level checks during pregnancy. Available at: https://epilepsypregnancy.com/for-clinicians/anti-seizure-medicationslevel-checks (accessed 03.12.2025).Shahid A., Hameed K., Zainab A., et al. Advances in pharmacogenomics: optimizing antiepileptic drug therapy for drugresistant epilepsy. Explor Neuroprot Ther. 2024; 4: 240–50. https://doi.org/10.37349/ent.2024.00080.Shahid A., Hameed K., Zainab A., et al. Advances in pharmacogenomics: optimizing antiepileptic drug therapy for drugresistant epilepsy. Explor Neuroprot Ther. 2024; 4: 240–50. https://doi.org/10.37349/ent.2024.00080.Balestrini S., Sisodiya S.M. Pharmacogenomics in epilepsy. Neurosci Lett. 2018; 667: 27–39. https://doi.org/10.1016/j.neulet.2017.01.014.Balestrini S., Sisodiya S.M. Pharmacogenomics in epilepsy. Neurosci Lett. 2018; 667: 27–39. https://doi.org/10.1016/j.neulet.2017.01.014.Yetgin A. Revolutionizing multi-omics analysis with artificial intelligence and data processing. Quant Biol. 2025; 13 (3): e70002. https://doi.org/10.1002/qub2.70002.Yetgin A. Revolutionizing multi-omics analysis with artificial intelligence and data processing. Quant Biol. 2025; 13 (3): e70002. https://doi.org/10.1002/qub2.70002.

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