asurgeryАмбулаторная хирургияAmbulatornaya khirurgiya = Ambulatory Surgery (Russia)2712-87412782-2591ООО «ГРУППА РЕМЕДИУМ»10.21518/akh2026-024asurgery-638Research ArticleОБМЕН ОПЫТОМEXCHANGE OF EXPERIENCE | PRACTICEНимесулид: фармакологические и клинические особенности действияNimesulid: Pharmacological and Clinical Profilehttps://orcid.org/0000-0001-6504-8169АфанасьевВ. В.AfanasyevV. V.

Афанасьев Василий Владимирович, д.м.н., профессор кафедры скорой медицинской помощи

195067, Санкт-Петербург, Пискаревский проспект, д. 47

Vasily V. Afanasyev, Dr. Sci. (Med.), Professor of the Department of Emergency Medicine

47, Piskarevsky Ave., St Petersburg, 197376

sobaka_liza@mail.ruhttps://orcid.org/0000-0003-2175-9801ПугачеваЕ. Л.PugachevaE. L.

Пугачева Екатерина Леонидовна, к.м.н., доцент кафедры неврологии

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Ekaterina L. Pugacheva, Cand. Sci. (Med.), Associate Professor of the Department of Neurology

6–8, Lev Tolstoy St., St Petersburg, 197022

fiakinsky@mail.ruhttps://orcid.org/0000-0003-4947-4779ИскраД. А.IskraD. A.

Искра Дмитрий Анатольевич, д.м.н., профессор, профессор кафедры медицинской реабилитации и спортивной медицины

194100, Санкт-Петербург, ул. Литовская, д. 2

Dmitrii A. Iskra, Dr. Sci. (Med.), Professor, Professor of the Department of Medical Rehabilitation and Sports Medicine

2, Litovskaya St., St. Petersburg, 194100

iskradm@mail.ruСеверо-Западный государственный медицинский университет имени И.И. МечниковаРоссияNorth-Western State Medical University named after I.I. MechnikovRussian FederationПервый Санкт-Петербургский государственный медицинский университет имени академика И.П. ПавловаРоссияPavlov First Saint Petersburg State Medical UniversityRussian FederationСанкт-Петербургский государственный педиатрический медицинский университетРоссияSaint-Petersburg State Pediatric Medical UniversityRussian Federation202607062026231179188Copyright © Афанасьев В.В., Пугачева Е.Л., Искра Д.А., 20262026Афанасьев В.В., Пугачева Е.Л., Искра Д.А.Afanasyev V.V., Pugacheva E.L., Iskra D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.a-surgeon.ru/jour/article/view/638

В обзоре представлены сведения по фармакодинамике, фармакокинетике и клинической фармакологии нестероидного противовоспалительного препарата (НПВП) нимесулид (НМС). Рассмотрены особенности химической структуры НМС и обусловленные ею механизмы действия, особенности клинических эффектов, отличающие НМС от его гомологов. Представлены особенности фармакодинамики: особенности ингибирования простагландинов НМС, cила взаимодействия НМС с циклооксигеназой (ЦОГ) ЦОГ-1 и ЦОГ-2, рассчитанная по концентрации полумаксимального ингибирования (коэффициент IC50.). Отмечена способность НМС снижать высвобождение фактора некроза опухоли-α (ФНО-α), наиболее агрессивного цитокина, что приводит к ингибированию активности урокиназы и активации плазминогена и препятствует дегенерации хрящевой ткани. Приведены данные по антиоксидантным свойствам НМС, его способности снижать уровень гистамина и изменять активность рецепторных систем: каннабиоидных и каинатных. Показаны перспективы использования НМС в онкологии в качестве средства антипролиферативной активности. Особенности строения его молекулы могут служить той фармакологической матрицей, которая может лежать в основе изыскания и изучения новых противоопухолевых средств, а сам НМС может служить фармакологическим зондом в оценке опухолевого роста. Представлена сравнительная эффективность с другими НПВП. Информационные ресурсы, использованные в статье: NCBI.NLM.NIH.GOV; Micromedex Inc., Tompson Series. Drugdex, 2017. British Pharmacological Society (resources and support for educators), RxList, 40 статей, содержащих данные по фармакодинамике нимесулида, из которых отобраны 25; 10 статей, содержащих информацию о фармакокинетике НМС, из которых отобраны 4; 30 статей, включающих информацию о фармакокинетических взаимодействиях НМС с препаратами других фармакологических групп, из которых отобраны 25 статей, 10 из которых были основаны на рандомизированных исследованиях, включивших более 2 000 испытуемых. Поиск осуществлялся по следующим ключевым словам: «нестероидные противовоспалительные препараты», «болевые синдромы и их лечение», «нимесулид», «циклооксигеназа», «простагландины», «арахидоновая кислота», «комбинации лекарственных веществ».

The review provides information on the pharmacodynamics, pharmacokinetics, and clinical pharmacology of the nonsteroidal anti-inflammatory drug (NSAID) nimesulide. The features of the chemical structure of nimesulide and its associated mechanisms of action, as well as the clinical effects that distinguish nimesulide from its homologues, are considered. Comparative efficacy with other NSAIDs is presented. The issues of clinical pharmacokinetics (pKа index; Cmax exposure levels; biotransformation; etc.) were discussed. The clinical part of the review includes comparative studies of nimesulide and its homologues, as well as combinations of nimesulide with drugs from other groups. The specificity of nimesulid induced hepatotoxicity is also discussed. Used info resources NCBI.NLM.NIH.GOV; Micromedex Inc., Tompson Series. Drugdex, 2017. British Pharmacological Society (resources and support for educators), RxList, 40 articles containing data on the pharmacodynamics of nimesulide, of which 25 were selected, 10 articles containing information on the pharmacokinetics of NMS, of which 4, 30 articles were selected, including information on the pharmacokinetic interactions of NMS with the medications from other pharmacological groups, from which 25 articles were selected, 10 of which were based on randomized trials involving more than 2,000 subjects. Scientific search was carried out using the following keywords: “nonsteroidal anti-inflammatory drugs”, “pain syndromes and their treatment”, “nimesulide”, “cyclooxygenase”, “prostaglandins”, “arachidonic acid”, “combinations of drugs”.

нестероидные противовоспалительные препаратыболевые синдромынимесулидциклооксигеназапростагландиныарахидоновая кислотакомбинации лекарственных веществnonsteroidal anti-inflammatory drugspain syndromesnimesulidecyclooxygenaseprostaglandinsarachidonic acidcombinations of drugsReferencesGarcia-Nieto R, Perez C, Chega A. Molecualar model of the interaction between nimesulide and human cyclooxygenase-2. Rheumatology. 1999;38(Suppl. 1):14–18. https://doi.org/10.1093/rheumatology/38.suppl_1.14.Garcia-Nieto R, Perez C, Chega A. Molecualar model of the interaction between nimesulide and human cyclooxygenase-2. Rheumatology. 1999;38(Suppl. 1):14–18. https://doi.org/10.1093/rheumatology/38.suppl_1.14.Гендугов ТА, Щербакова ЛИ, Глушко АА, Кодониди ИП, Сочнев ВС. Изучение взаимодействия производных 4-оксопиримидина с активным центром циклооксигеназы-2 методом молекулярной динамики. Современные проблемы науки и образования. 2015;(2):503. Режим доступа: https://science-education.ru/ru/article/view?id=22796.Gendugov TA, Shcherbakova LI, Glushko AA, Kodonidi IP, Sochnev VS. Study of 4-oxopirimidine derivatives interaction with the active site of cyclooxygenase-2 using molecular dynamics. Modern Problems of Science and Education. 2015;(2):503. (In Russ.) Available at: https://science-education.ru/ru/article/view?id=22796.Matta C, Ciarcia S, Muhinbo A, Coluzzi F. Нимесулид: 25 лет спустя. РМЖ. 2012;(30):1527–1532. Режим доступа: https://www.rmj.ru/articles/revmatologiya/Nimesulid_25_let_spustya/.Matta C, Ciarcia S, Muhinbo A, Coluzzi F. Nimesulid: 25 years later. RMJ.2012;(30):1527–1532. (In Russ.) Available at: https://www.rmj.ru/articles/revmatologiya/Nimesulid_25_let_spustya/.Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficacy in inflammation and pain states. Drugs. 1988;36(6):732–753. https://doi.org/10.2165/00003495-198836060-00004.Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficacy in inflammation and pain states. Drugs. 1988;36(6):732–753. https://doi.org/10.2165/00003495-198836060-00004.Rufer C, Schillinger E, Bottcher I, Repenthin W, Hermann C. Mode of action of anti-inflammatory methane sulfonanilides. Biochem Pharmacol. 1982;31(22):3591–3596. https://doi.org/10.1016/0006-2952(82)90580-9.Rufer C, Schillinger E, Bottcher I, Repenthin W, Hermann C. Mode of action of anti-inflammatory methane sulfonanilides. Biochem Pharmacol. 1982;31(22):3591–3596. https://doi.org/10.1016/0006-2952(82)90580-9.Dallegri F, Ottonello L, Dapino P, Sfcchetti C. Effect of nonsteroidal anti-inflammatory drugs on the neutrophil promoted inactivation of alpha-1-proteinase inhibitor. J Rheumatol. 1992;19(3):419–423. Available at: https://pubmed.ncbi.nlm.nih.gov/1578457.Dallegri F, Ottonello L, Dapino P, Sfcchetti C. Effect of nonsteroidal anti-inflammatory drugs on the neutrophil promoted inactivation of alpha-1-proteinase inhibitor. J Rheumatol. 1992;19(3):419–423. Available at: https://pubmed.ncbi.nlm.nih.gov/1578457.Candelario-Jalil E, Mhadu N, Gonzalrz-Falcon A, Garcia-Carbrera M, Munoz E, Leon OS, Fiebich BL. Effects of the cyclooxygenase-2 inhibitor nimesulide on cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion in the rat. J Neuroinflammation. 2005;2(1):3. https://doi.org/10.1186/1742-2094-2-3.Candelario-Jalil E, Mhadu N, Gonzalrz-Falcon A, Garcia-Carbrera M, Munoz E, Leon OS, Fiebich BL. Effects of the cyclooxygenase-2 inhibitor nimesulide on cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion in the rat. J Neuroinflammation. 2005;2(1):3. https://doi.org/10.1186/1742-2094-2-3.Duffy T, Belton O, Bresnihan B, FitzGerald O, FitzGerald D. Inhibition of PGE2 production by nimesulide compared with diclofenac in the acutely inflamed joint of patients with arthritis. Drugs. 2003;63(Suppl. 1):31–36. https://doi.org/10.2165/00003495-200363001-00005.Duffy T, Belton O, Bresnihan B, FitzGerald O, FitzGerald D. Inhibition of PGE2 production by nimesulide compared with diclofenac in the acutely inflamed joint of patients with arthritis. Drugs. 2003;63(Suppl. 1):31–36. https://doi.org/10.2165/00003495-200363001-00005.Candelario-Jalil E, Sonia León O. Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain homogenates. BMC Pharmacol. 2003;3:7. https://doi.org/10.1186/1471-2210-3-7.Candelario-Jalil E, Sonia León O. Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain homogenates. BMC Pharmacol. 2003;3:7. https://doi.org/10.1186/1471-2210-3-7.Lindgren СA, Newman ZL, Morford JJ, Ruan SB, Battani KA, Su Z. Cyclooxygenase-2, prostaglandin E2 glycerol ester and nitric oxide are involved in muscarine-induced presynaptic enhancement at the vertebrate neuromuscular junction. J Physiol. 2013;591(19):4749–4764. https://doi.org/10.1113/jphysiol.2013.256727.Lindgren СA, Newman ZL, Morford JJ, Ruan SB, Battani KA, Su Z. Cyclooxygenase-2, prostaglandin E2 glycerol ester and nitric oxide are involved in muscarine-induced presynaptic enhancement at the vertebrate neuromuscular junction. J Physiol. 2013;591(19):4749–4764. https://doi.org/10.1113/jphysiol.2013.256727.França-Neto A, Couto GK, Xavier FE, Rossoni LV. Cyclooxygenase-2 is a critical determinant of angiotensin II-induced vascular remodeling and stiffness in resistance arteries of ouabain-treated rats. J Hypertens. 2022;40(11):2180–2191. https://doi.org/10.1097/HJH.0000000000003242.França-Neto A, Couto GK, Xavier FE, Rossoni LV. Cyclooxygenase-2 is a critical determinant of angiotensin II-induced vascular remodeling and stiffness in resistance arteries of ouabain-treated rats. J Hypertens. 2022;40(11):2180–2191. https://doi.org/10.1097/HJH.0000000000003242.Ferreira SH. The role of interleukins and nitric oxide in the mediation of inflammatory pain and its control by peripheral analgesics. Drugs. 1993;46(Suppl. 1):1–9. https://doi.org/10.2165/00003495-199300461-00003.Ferreira SH. The role of interleukins and nitric oxide in the mediation of inflammatory pain and its control by peripheral analgesics. Drugs. 1993;46(Suppl. 1):1–9. https://doi.org/10.2165/00003495-199300461-00003.Pelletier JP, Mineau F, Fernandes JC, Kiansa K, Ranger P, Martel-Peletier J. Two NSAIDs nimesulid and naproxen can reduce the synthesis of urokinase anf IL-6 whilr increasing PAI-1 in human OA synovial fibroblasts. Clin Exp Reumatol. 1997;15(4):393–398. Available at: https://pubmed.ncbi.nlm.nih.gov/9272300.Pelletier JP, Mineau F, Fernandes JC, Kiansa K, Ranger P, Martel-Peletier J. Two NSAIDs nimesulid and naproxen can reduce the synthesis of urokinase anf IL-6 whilr increasing PAI-1 in human OA synovial fibroblasts. Clin Exp Reumatol. 1997;15(4):393–398. Available at: https://pubmed.ncbi.nlm.nih.gov/9272300.Facino M ,Carinin M, Aldini G. Antioxidant activity of nimesulide and its main metabolites. Drugs. 1993;46(Suppl. 1):15–21. https://doi.org/10.2165/00003495-199300461-00005.Facino M ,Carinin M, Aldini G. Antioxidant activity of nimesulide and its main metabolites. Drugs. 1993;46(Suppl. 1):15–21. https://doi.org/10.2165/00003495-199300461-00005.Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin Pharmacokinet. 1998;35(4):247–274. https://doi.org/10.2165/00003088-199835040-00001.Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin Pharmacokinet. 1998;35(4):247–274. https://doi.org/10.2165/00003088-199835040-00001.Bianco S, Robuschi M, Petrigni G, Scuri M, Pieroni MG, Refin RM et al. Efficacy and tolerability of nimesulide in asthmatic patients intolerant to aspirin. Drugs. 1993;46(Suppl. 1):115–120. https://doi.org/10.2165/00003495-199300461-00024.Bianco S, Robuschi M, Petrigni G, Scuri M, Pieroni MG, Refin RM et al. Efficacy and tolerability of nimesulide in asthmatic patients intolerant to aspirin. Drugs. 1993;46(Suppl. 1):115–120. https://doi.org/10.2165/00003495-199300461-00024.Staniaszek LE, Norris LM, Kendal DA, Barrett DA, Chapman V. Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids. Br J Pharmacol. 2010;160(3):669–676. https://doi.org/10.1111/j.1476-5381.2010.00703.Staniaszek LE, Norris LM, Kendal DA, Barrett DA, Chapman V. Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids. Br J Pharmacol. 2010;160(3):669–676. https://doi.org/10.1111/j.1476-5381.2010.00703.Hermanson D, Xartly H, Gamble-George J, Brown N, Shonesy BC, Kingsley PJ et al. Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat Neurosci. 2013;16(9):1291–1298. https://doi.org/10.1038/nn.3480.Hermanson D, Xartly H, Gamble-George J, Brown N, Shonesy BC, Kingsley PJ et al. Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat Neurosci. 2013;16(9):1291–1298. https://doi.org/10.1038/nn.3480.Котова ОВ. Влияние на эндоканнабиоидные системы: один из возможных механизмов действия нимесулида. Фармактека. 2012;19(20):30–32. Режим доступа: https://journals.eco-vector.com/2073-4034/article/view/280140.Kotova OV. Effect on endocannabioid systems: one of the possible mechanisms of action of nimesulide. Farmateka. 2012;19(20):30–32. (In Russ.) Available at: https://journals.eco-vector.com/2073-4034/article/view/280140.Гриднева ГИ. Нимесулид: разнообразие терапевтических перспектив. Эффективная фармакотерапия. 2019;15(8):18–22. https://doi.org/10.33978/2307-3586-2019-15-8-18-22.Gridneva GI. Nimesulide: a Variety of Therapeutic Perspectives. Effective Pharmacotherapy. 2019;15(8):18–22. (In Russ.) https://doi.org/10.33978/2307-3586-2019-15-8-18-22.Blaker А, Rodriguez Е, Yamamoto BK. Neurotoxicity to dopamine neurons after the serial exposure to alcohol and methamphetamine: Protection by COX-2 antagonism. Brain Behav Immun. 2019;81:317–328. https://doi.org/10.1016/j.bbi.2019.06.028.Blaker А, Rodriguez Е, Yamamoto BK. Neurotoxicity to dopamine neurons after the serial exposure to alcohol and methamphetamine: Protection by COX-2 antagonism. Brain Behav Immun. 2019;81:317–328. https://doi.org/10.1016/j.bbi.2019.06.028.Vunnam YL, Yong MC, Liao EE, Lo C, Huber E, Been M et al. Nimesulide, a COX-2 inhibitor, sensitizes pancreatic cancer cells to TRAILinduced apoptosis by promoting DR5 clustering. Cancer Biol Ther. 2023;24(1):2176692. https://doi.org/10.1080/15384047.2023.2176692.Vunnam YL, Yong MC, Liao EE, Lo C, Huber E, Been M et al. Nimesulide, a COX-2 inhibitor, sensitizes pancreatic cancer cells to TRAILinduced apoptosis by promoting DR5 clustering. Cancer Biol Ther. 2023;24(1):2176692. https://doi.org/10.1080/15384047.2023.2176692.Tomaz V, Griesi-Oliveira K, Puga R, Conti BJ, Santos FPS, Hamerschlak N, Campregher PV. Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia. Front Oncol. 2022;12:874168. https://doi.org/10.3389/fonc.2022.874168.Tomaz V, Griesi-Oliveira K, Puga R, Conti BJ, Santos FPS, Hamerschlak N, Campregher PV. Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia. Front Oncol. 2022;12:874168. https://doi.org/10.3389/fonc.2022.874168.Jian YS, Chen CW, Lin CA, Yu HP, Lin HY, Liao MY et al. Hyaluronic acid-nimesulide conjugates as anticancer drugs against CD44- overexpressing HT-29 colorectal cancer in vitro and in vivo. Int J Nanomedicine. 2017;12:2315–2333. https://doi.org/10.2147/IJN.S120847.Jian YS, Chen CW, Lin CA, Yu HP, Lin HY, Liao MY et al. Hyaluronic acid-nimesulide conjugates as anticancer drugs against CD44- overexpressing HT-29 colorectal cancer in vitro and in vivo. Int J Nanomedicine. 2017;12:2315–2333. https://doi.org/10.2147/IJN.S120847.Reinsford R (ed.). Nimesulide. Actions and Uses. Birkhauser; 2005. 449 p.Reinsford R (ed.). Nimesulide. Actions and Uses. Birkhauser; 2005. 449 p.Castoldi D, Monzani V, Tofanetti O. Simultaneous determination of nimesulide and hydroxynimesulide in human plasma and urine by high-performance liquid chromatography. J Chromatogr. 1988;425(2):413–418. https://doi.org/10.1016/0378-4347(88)80048-3.Castoldi D, Monzani V, Tofanetti O. Simultaneous determination of nimesulide and hydroxynimesulide in human plasma and urine by high-performance liquid chromatography. J Chromatogr. 1988;425(2):413–418. https://doi.org/10.1016/0378-4347(88)80048-3.D'Apuzzo V, Monti T. Pilot study of the antipyretic and analgesic activity of nimesulide paediatric suppositories. Drugs Exp Clin Res. 1992;18(2):63–68. Available at: https://pubmed.ncbi.nlm.nih.gov/1644012.D'Apuzzo V, Monti T. Pilot study of the antipyretic and analgesic activity of nimesulide paediatric suppositories. Drugs Exp Clin Res. 1992;18(2):63–68. Available at: https://pubmed.ncbi.nlm.nih.gov/1644012.Milvio C. Nimesulide for the treatment of painful inflammatory process in the ear, nose and throat areas: a double blind controlled trial with benzydamine. J Int Med Res. 1984;12(6):327–332. https://doi.org/10.1177/030006058401200602.Milvio C. Nimesulide for the treatment of painful inflammatory process in the ear, nose and throat areas: a double blind controlled trial with benzydamine. J Int Med Res. 1984;12(6):327–332. https://doi.org/10.1177/030006058401200602.Ulukol B, Köksal Y, Cin S. Assessment of the efficacy and safety of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections. Eur J Clin Pharmacol. 1999;55(9):615–618. https://doi.org/10.1007/s002280050681.Ulukol B, Köksal Y, Cin S. Assessment of the efficacy and safety of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections. Eur J Clin Pharmacol. 1999;55(9):615–618. https://doi.org/10.1007/s002280050681.Cunietti E, Monti M, Viganò A, D'Aprile E, Saligari A, Scafuro E, Scaricabarozzi I. A Comparison of Nimesulide vs Paracetamol in the Treatment of Pyrexia in the Elderly. Drugs. 1993;46(Suppl. 1):124–126. https://doi.org/10.2165/00003495-199300461-00026.Cunietti E, Monti M, Viganò A, D'Aprile E, Saligari A, Scafuro E, Scaricabarozzi I. A Comparison of Nimesulide vs Paracetamol in the Treatment of Pyrexia in the Elderly. Drugs. 1993;46(Suppl. 1):124–126. https://doi.org/10.2165/00003495-199300461-00026.Cappella L, Guerra A, Laudizi L, Gavazzyti GV. Efficacy and tolerability of nimesulide and lysine-acetylsalicylate in the treatment of paediatric acute upper respiratory tract inflammation. Drugs. 1993;46(Suppl. 1):222–225. https://doi.org/10.2165/00003495-199300461-00057.Cappella L, Guerra A, Laudizi L, Gavazzyti GV. Efficacy and tolerability of nimesulide and lysine- acetylsalicylate in the treatment of paediatric acute upper respiratory tract inflammation. Drugs. 1993;46(Suppl. 1):222–225. https://doi.org/10.2165/00003495-199300461-00057.Corli O, Cozzolino A, Scaricabarozzi I. Nimesulide and diclofenac in the control of cancer-related pain. Drugs. 1993;46(Suppl. 1):152–155. https://doi.org/10.2165/00003495-199300461-00036.Corli O, Cozzolino A, Scaricabarozzi I. Nimesulide and diclofenac in the control of cancer-related pain. Drugs. 1993;46(Suppl. 1):152–155. https://doi.org/10.2165/00003495-199300461-00036.Facchinetti F, Piccinini F, Sgarbi L, Renzetti O. Nimesulide in the treatment of primary dysmenorrhea: a double blind study versus diclofenac. Drugs Today. 2001;37(Suppl. B):39–45.Facchinetti F, Piccinini F, Sgarbi L, Renzetti O. Nimesulide in the treatment of primary dysmenorrhea: a double blind study versus diclofenac. Drugs Today. 2001;37(Suppl. B):39–45.Sengupta S, Velpandian T, Kabir SR, Gupta SK. Analgesic efficacy and pharmacokinetics of topical nimesulide gel in healthy human volunteers: double-blind comparison with piroxicam, diclofenac and placebo. Eur J Clin Pharmacol. 1998;54(7):541–547. https://doi.org/10.1007/s002280050510.Sengupta S, Velpandian T, Kabir SR, Gupta SK. Analgesic efficacy and pharmacokinetics of topical nimesulide gel in healthy human volunteers: double-blind comparison with piroxicam, diclofenac and placebo. Eur J Clin Pharmacol. 1998;54(7):541–547. https://doi.org/10.1007/s002280050510.Ramella G, Costagli V, Vetere M, Capra C, Casella G, Sogni A, Scaricabarozzi I. Comparison of nimesulide and diclofenac in the prevention and treatment of painful inflammatory postoperative complications of general surgery. Drugs. 1993;46(Suppl. 1):159–161. https://doi.org/10.2165/00003495-199300461-00038.Ramella G, Costagli V, Vetere M, Capra C, Casella G, Sogni A, Scaricabarozzi I. Comparison of nimesulide and diclofenac in the prevention and treatment of painful inflammatory postoperative complications of general surgery. Drugs. 1993;46(Suppl. 1):159–161. https://doi.org/10.2165/00003495-199300461-00038.Rainsford KD. Nimesulide: overview of properties and applications. Drugs Today. 2001;37(Suppl. B):3–7.Rainsford KD. Nimesulide: overview of properties and applications. Drugs Today. 2001;37(Suppl. B):3–7.Rossoni G, Berti F, Buschi A, Villa LM, Bella DD. New data concerning the antianaphylactic and antihistaminic activity of nimesulide. Drugs. 1993;46(Suppl. 1):S22– S28. https://doi.org/10.2165/00003495-199300461-00006.Rossoni G, Berti F, Buschi A, Villa LM, Bella DD. New data concerning the antianaphylactic and antihistaminic activity of nimesulide. Drugs. 1993;46(Suppl. 1):S22– S28. https://doi.org/10.2165/00003495-199300461-00006.Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic еfficacy in inflammation and pain states. Drugs. 1988;36(6):732–753. https://doi.org/10.2165/00003495-198836060-00004.Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic еfficacy in inflammation and pain states. Drugs. 1988;36(6):732–753. https://doi.org/10.2165/00003495-198836060-00004.Pohjolainen T, Jekunen A, Autio L, Vuorela H. Treatment of acute low back pain with the COX-2-selective anti-inflammatory drug nimesulide: results of a randomized, double-blind comparative trial versus ibuprofen. Spine. 2000;25(12):1579–1585. https://doi.org/10.1097/00007632-200006150-00019.Pohjolainen T, Jekunen A, Autio L, Vuorela H. Treatment of acute low back pain with the COX-2-selective anti-inflammatory drug nimesulide: results of a randomized, double-blind comparative trial versus ibuprofen. Spine. 2000;25(12):1579–1585. https://doi.org/10.1097/00007632-200006150-00019.Toscani F, Gallucci M, Scaricabarozzi I. Nimesulide in the treatment of advanced cancer pain: double-blind comparison with naproxen. Drugs. 1993;46(Suppl. 1):156–158. https://doi.org/10.2165/00003495-199300461-00037.Toscani F, Gallucci M, Scaricabarozzi I. Nimesulide in the treatment of advanced cancer pain: double-blind comparison with naproxen. Drugs. 1993;46(Suppl. 1):156–158. https://doi.org/10.2165/00003495-199300461-00037.Fossaluzza V, Montagnani G. Effcacy and tolerability of nimesulide in elderly patients with osteoarthritis: double-blind trial versus naproxen. J Int Med Res. 1989;17(3):295–303. https://doi.org/10.1177/030006058901700313.Fossaluzza V, Montagnani G. Effcacy and tolerability of nimesulide in elderly patients with osteoarthritis: double-blind trial versus naproxen. J Int Med Res. 1989;17(3):295–303. https://doi.org/10.1177/030006058901700313.Kriegel W, Kor KJ, Ehrlich JC, Lehnhardt K. Double-blind study comparing the long-term effcacy of the COX-2 inhibitor nimesulide and naproxen in patients with osteoarthritis. Int J Clin Pract. 2001;55(8):510–514. https://doi.org/10.1111/j.1742-1241.2001.tb11112.x.Kriegel W, Kor KJ, Ehrlich JC, Lehnhardt K. Double-blind study comparing the long-term effcacy of the COX-2 inhibitor nimesulide and naproxen in patients with osteoarthritis. Int J Clin Pract. 2001;55(8):510–514. https://doi.org/10.1111/j.1742-1241.2001.tb11112.x.Каратеев АЕ, Насонов ЕЛ, Ивашкин ВТ, Мартынов АИ, Яхно НН, Арутюнов ГП и др. Рациональное использование нестероидных противовоспалительных препаратов. Клинические рекомендации. Научно-практическая ревматология. 2018;56(Прил. 1):1–29. https://doi.org/10.14412/1995-4484-2018-1-29.Karateev AE, Nasonov EL, Ivashkin VT, Martynov AI, Yakhno NN, Arutyunov GP et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical guidelines. Rheumatology Science and Practice. 2018;56(Suppl. 1):1–29. (In Russ.) https://doi.org/10.14412/1995-4484-2018-1-29.Scheinberg M, Pott Júnior H, Macêdo EA, Bocchi de Oliveira MF, Ecclissato C, Amazonas RB. Efficacy and safety of a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for pain relief in patients with osteoarticular diseases and dyspeptic symptoms. Drug Des Devel Ther. 2018;12:2775–2783. https://doi.org/10.2147/DDDT.S172068.Scheinberg M, Pott Júnior H, Macêdo EA, Bocchi de Oliveira MF, Ecclissato C, Amazonas RB. Efficacy and safety of a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for pain relief in patients with osteoarticular diseases and dyspeptic symptoms. Drug Des Devel Ther. 2018;12:2775–2783. https://doi.org/10.2147/DDDT.S172068.Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficacy in inflammation and pain states. Drugs. 1988;36(6):732–753. https://doi.org/10.2165/00003495-198836060-00004.Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficacy in inflammation and pain states. Drugs. 1988;36(6):732–753. https://doi.org/10.2165/00003495-198836060-00004.Каратеев АЕ. Нимесулид: достоинства превышают недостатки. Трудный пациент. 2012;10(4):42–49. Режим доступа: https://med-click.ru/uploads/files/docs/nimesulid-dostoinstva-prevyshayut-nedostatki.pdfKarateev AE. Nimesulide: advantages overcomes shortcomings. Trudnyi Patsient. 2012;10(4):42–49. (In Russ.) Available at: https://med-click.ru/uploads/files/docs/nimesulid-dostoinstva-prevyshayut-nedostatki.pdfBoelsterli U. Mechanisms of NSAID-induced hepatotoxicity: focus on nimesulide. Drug Saf. 2002;25(9):633–648. https://doi.org/10.2165/00002018-200225090-00003.Boelsterli U. Mechanisms of NSAID-induced hepatotoxicity: focus on nimesulide. Drug Saf. 2002;25(9):633–648. https://doi.org/10.2165/00002018-200225090-00003.Kulkarni S. On the safety of nimesulide, a preferential COX-2 inhibitor. Curr Sci. 2002;83:1442–1443.Kulkarni S. On the safety of nimesulide, a preferential COX-2 inhibitor. Curr Sci. 2002;83:1442–1443.Rainsford K. An analysis from clinico-epidemiological data of the principal adverse events from the COX-2 selective NSAID, nimesulide, with particular reference to hepatic injury. Inflammopharmacology. 1998;6(3):203–221. https://doi.org/10.1007/s10787-998-0020-6.Rainsford K. An analysis from clinico-epidemiological data of the principal adverse events from the COX-2 selective NSAID, nimesulide, with particular reference to hepatic injury. Inflammopharmacology. 1998;6(3):203–221. https://doi.org/10.1007/s10787-998-0020-6.Каратеев АЕ, Насонова ВА. НПВП-ассоциированная гепатопатия: проблема нимесулида. Научно-практическая ревматология. 2003;41(4):87–91. https://doi.org/10.14412/1995-4484-2003-1342.Karateev AV, Nassonova VA. NSAID-associated gepathopathy: nimesulid problem. Rheumatology Science and Practice. 2003;41(4):87–91. (In Russ.) https://doi.org/10.14412/1995-4484-2003-1342.Zhou L, Pang X, Xie C, Zhong D, Chen X. Chemical and Enzymatic Transformations of Nimesulide to GSH Conjugates through Reductive and Oxidative Mechanisms. Chem Res Toxicol. 2015;28(12):2267–2277. https://doi.org/10.1021/acs.chemrestox.5b00290.Zhou L, Pang X, Xie C, Zhong D, Chen X. Chemical and Enzymatic Transformations of Nimesulide to GSH Conjugates through Reductive and Oxidative Mechanisms. Chem Res Toxicol. 2015;28(12):2267–2277. https://doi.org/10.1021/acs.chemrestox.5b00290.Сатырова ТВ. Ацетиляторный статус: современный взгляд на проблему (обзор литературы). Проблемы здоровья и экологии. 2009;(4):32–36. https://doi.org/10.51523/2708-6011.2009-6-4-5.Satyrova TV. The acetylated status: present-day point of view on the subject (references review). Health and Ecology Issues. 2009;(4):31–36. (In Russ.) https://doi.org/10.51523/2708-6011.2009-6-4-5.Zhou L, Pang X, Jiang L, Zhong D, Chen X. Nimesulide and 4'-Hydroxynimesulide as Bile Acid Transporters Inhibitors Are Contributory Factors for Drug-Induced Cholestasis. Drug Metab Dispos. 2017;45(5):441–448. https://doi.org/10.1124/dmd.116.074104.Zhou L, Pang X, Jiang L, Zhong D, Chen X. Nimesulide and 4'-Hydroxynimesulide as Bile Acid Transporters Inhibitors Are Contributory Factors for Drug-Induced Cholestasis. Drug Metab Dispos. 2017;45(5):441–448. https://doi.org/10.1124/dmd.116.074104.Хлынова ОВ, Маев ИВ, Тарасова ЛВ, Долгушина АИ, Барановский АЮ, Минушкин ОН и др. Лекарственные поражения печени: клинические рекомендации. 2019.Хлынова ОВ, Маев ИВ, Тарасова ЛВ, Долгушина АИ, Барановский АЮ, Минушкин ОН и др. Лекарственные поражения печени: клинические рекомендации. 2019.Li F, Chordia M, Huang T, Macdonald TL. In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinone formation and conjugation. Chem Res Toxicol. 2009;22(1):72–80. https://doi.org/10.1021/tx800152r.Li F, Chordia M, Huang T, Macdonald TL. In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinone formation and conjugation. Chem Res Toxicol. 2009;22(1):72–80. https://doi.org/10.1021/tx800152r.Афанасьев ВВ, Баранцевич ЕР, Вишневецкая ТП. Азбука нейроцитопротекции. СПб.: Стелла; 2016. 279 с.Афанасьев ВВ, Баранцевич ЕР, Вишневецкая ТП. Азбука нейроцитопротекции. СПб.: Стелла; 2016. 279 с.

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