biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Productsbiopreparat-62Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЭкспериментальное исследование фармакодинамики моноклональных антител к α4β1-интегрину на морских свинкахExperimental study of the pharmacokinetics of monoclonal antibodies to α4β1-integrin in guinea pigsКрапивинБ. Н.KrapivinB. N.

Старший научный сотрудник отдела доклинических испытаний лекарственных средств

Senior researcher of the Department of preclinical trials of drug products

krapivin@biocad.ruГончароваО. В.GoncharovaO. V.

Заведующая отделом рекомбинантных продуцентов, канд. биол. наук

Head of the Department of recombinant proteins. Candidate of Biological Sciences

noemail@neicon.ruМорозоваЕ. Л.MorozovaE. L.

Руководитель отдела доклинических испытаний лекарственных средств

Head of the Department of preclinical trials of drug products

noemail@neicon.ruЗАО «БИОКАД»РоссияCJSC «BIOCAD»Russian Federation201620022018163179181Copyright © Крапивин Б.Н., Гончарова О.В., Морозова Е.Л., 20182018Крапивин Б.Н., Гончарова О.В., Морозова Е.Л.Krapivin B.N., Goncharova O.V., Morozova E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/62

В статье представлен материал по оценке фармакодинамики моноклональных антител к α4β1-интегрину на морских свинках. Исследовано воздействие препарата на абсолютное содержание лейкоцитов периферической крови после однократного внутрибрюшинного введения в трех дозах. Показано, что внутрибрюшинное введение препарата в дозах 30, 60 и 120 мг/кг вызывает двукратное повышение содержания лейкоцитов уже в первые сутки после введения, достигая максимальных значений к 6 суткам. Впоследствии к 11-18 суткам, в зависимости от дозы препарата, содержание лейкоцитов постепенно снижается до контрольных значений.

This article presents the data on pharmacodynamics evaluation of monoclonal antibodies to α4β1-integrin in guinea pigs. The effect on total content of peripheral blood leukocytes after a single intraperitoneal injection of three doses of the drug has been studied. It was shown that intraperitoneal injection of the drug at doses of 30, 60, and 120 mg/kg causes a twofold increase in the content of leukocytes in the first hours after the administration, reaching a maximum value to 6th day. Subsequently 11-18 days, depending on dose, leukocytes content gradually decreased to control values.

моноклональные антитела к α4β1-интегринурассеянный склерозфармакодинамикаэкспериментальные исследованияmonoclonal antibodies to α4β1-integrinmultiple sclerosispharmacodynamicsexperimental researchReferencesМументалер М, Маттле Х. Неврология. 3-е изд. М.: МЕДпресс-информ; 2011.Mumentaler Ì, Mattle H. Neurology. 3rd ed. Moscow: MEDpress-Inform; 2011 (in Russian).Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol. 2007; 6(10): 903-12.Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol. 2007; 6(10): 903–12.Goodin DS, Cohen BA, O’Connor P, et al. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008; 71: 766-73.Goodin DS, Cohen BA, O’Connor P, et al. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008; 71: 766–73.Lobb RR, Hemler ME. The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest. 1994; 94: 1722-8.Lobb RR, Hemler ME. The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest. 1994; 94: 1722–8.Brocke S, Piercy C, Steinman L, et al. Antibodies to CD44 and integrin alpha4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment. Proc Natl Acad Sci USA 1999; 96: 6896-901.Brocke S, Piercy C, Steinman L, et al. Antibodies to CD44 and integrin alpha4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment. Proc Natl Acad Sci USA 1999; 96: 6896–901.Rice GP, Hartung HP, Calabresi PA. Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology 2005; 64: 1336-42.Rice GP, Hartung HP, Calabresi PA. Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology 2005; 64: 1336–42.Ley K, Laudanna C, Cybulsky MI, et al. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007; (7): 678-89.Ley K, Laudanna C, Cybulsky MI, et al. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007; (7): 678–89.Wehner NG, Gasper C, Shopp G, Nelson J, Draper K, Parker S, Clarke J. Immunotoxicity profile of natalizumab. J Immunotoxicol. 2009; 6(2): 115-29.Wehner NG, Gasper C, Shopp G, Nelson J, Draper K, Parker S, Clarke J. Immunotoxicity profile of natalizumab. J Immunotoxicol. 2009; 6(2): 115–29.Трухачева НВ. Математическая статистика в медико-биологических исследованиях с применением пакета Statistica. М.: ГЭОТАР-Медиа; 2013.Truhacheva NV. Mathematical Statistics in biomedical research with Statistica package. Moscow: GEOTAR-Media; 2013 (in Russian).

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