pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2022-10-6-562-572pmedpharm-1221Research ArticleФАРМАКОЛОГИЯ И КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯPHARMACOLOGY AND CLINICAL PHARMACOLOGYИССЛЕДОВАНИЕ БИОЭКВИВАЛЕНТНОСТИ ВОСПРОИЗВЕДЕННОГО ПРЕПАРАТА МОЛНУПИРАВИРА У ЗДОРОВЫХ ДОБРОВОЛЬЦЕВBIOEQUIVALENCE STUDY OF GENERIC MOLNUPIRAVIR IN HEALTHY VOLUNTEERShttps://orcid.org/0000-0003-2503-4402ВасилюкВ. Б.VasilyukV. B.

доктор медицинских наук, управляющий ООО «НИЦ Эко-безопасность»; профессор кафедры токсикологии, экстремальной и водолазной медицины ФГБОУ ВО СЗГМУ им. И.И. Мечникова Минздрава России

196143, Россия, г. Санкт-Петербург, пр-т Юрия Гагарина, д. 65

191015, Россия, г. Санкт-Петербург, ул. Кирочная, д. 41

Doctor of Sciences (Medicine), Managing Director of “Eco-Safety Scientific Research Center”, Professor of the Department of Toxicology, Extreme and Diving Medicine, North-Western State Medical University n.a. I.I. Mechnikov

65, Yuri Gagarin Ave., St. Petersburg, Russia, 196143

41, Kirochnaya Str., St. Petersburg, Russia, 191015

vasilyuk_vb@ecosafety.ruhttps://orcid.org/0000-0003-1074-5551БородулеваА. Ю.BorodulevaA. Yu.

старший химик-аналитик ООО «Экзактэ Лабс»

117246, Россия, Москва, Научный проезд, д. 20, стр. 2

Senior Analytical Chemist, “Exacte Labs”

Bldg 2, 20, Nauchny driveway, Moscow, Russia, 117246

anna.boroduleva@exactelabs.comhttps://orcid.org/0000-0003-3634-596XСоболевП. Д.SobolevP. D.

заведующий лабораторией биоаналитики ООО «Экзактэ Лабс»

117246, Россия, Москва, Научный проезд, д. 20, стр. 2

Head of the Laboratory of Bioanalytics, “Exacte Labs”

Bldg 2, 20, Nauchny driveway, Moscow, Russia, 117246

pavel.sobolev@exactelabs.comhttps://orcid.org/0000-0002-5719-0787НикифороваА. Г.NikiforovaA. G.

руководитель отдела биоаналитики ООО «Экзактэ Лабс»

117246, Россия, Москва, Научный проезд, д. 20, стр. 2

Head of the Bioanalytics Department, “Exacte Labs”

Bldg 2, 20, Nauchny driveway, Moscow, Russia, 117246

aiyyna.nikiforova@exactelabs.comhttps://orcid.org/0000-0002-8934-8884МозговаяВ. Г.MozgovayaV. G.

научный советник АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

 Scientific Adviser, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

mozgovay@rpharm.ruhttps://orcid.org/0000-0002-8735-7429ФилонО. В.FilonO. V.

директор департамента АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

Department Director, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

ov.filon@rpharm.ruhttps://orcid.org/0000-0002-7028-0496ЗинковскаяА. В.ZinkovskayaA. V.

руководитель группы биостатистики департамента доклинической и клинической разработки АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

Head of the Biostatistics Group of the Department of Preclinical and Clinical Development, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

zinkovskaya@rpharm.ruhttps://orcid.org/0000-0003-2818-6583ИгнатьевВ. Г.IgnatievV. G.

кандидат медицинских наук, генеральный директор АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

Candidate of Sciences (Medicine), General Director, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

info@rpharm.ruhttps://orcid.org/0000-0003-2685-1623СамсоновМ. Ю.SamsonovM. Yu.

кандидат медицинских наук, доцент, медицинский директор АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

Candidate of Sciences (Medicine), Associate Professor, Medical Director, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

samsonov@rpharm.ruhttps://orcid.org/0000-0002-2536-296XКозловаИ. С.KozlovaI. S.

медицинский писатель АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

Medical Writer, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

is.kozlova@rpharm.ruhttps://orcid.org/0000-0001-5848-0869ХанонинаЕ. К.KhanoninaE. K.

младший специалист АО «Р-Фарм»

123154, Россия, г. Москва, ул. Берзарина, д. 19, корп. 1

Junior Specialist, “R-Pharm”

Bldg 1, 19, Berzarin Str., Moscow, Russia, 123154

khanonina@rphapm.ruОбщество с ограниченной ответственностью «Научно-исследовательский центр Эко-безопасность» (ООО «НИЦ Эко-безопасность»); Федеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет имени И.И. Мечникова» Министерства здравоохранения Российской ФедерацииРоссияLimited Liability Company “Eco-Safety Scientific Research Center”; North-Western State Medical University named after I.I. MechnikovRussian FederationОбщество с ограниченной ответственностью «Экзактэ Лабс»РоссияLimited Liability Company “Exacte Labs”Russian FederationАкционерное общество «Р-Фарм»РоссияJoint-Stock Company “R-Pharm”Russian Federation202213022023106562572Copyright © Василюк В.Б., Бородулева А.Ю., Соболев П.Д., Никифорова А.Г., Мозговая В.Г., Филон О.В., Зинковская А.В., Игнатьев В.Г., Самсонов М.Ю., Козлова И.С., Ханонина Е.К., 20232023Василюк В.Б., Бородулева А.Ю., Соболев П.Д., Никифорова А.Г., Мозговая В.Г., Филон О.В., Зинковская А.В., Игнатьев В.Г., Самсонов М.Ю., Козлова И.С., Ханонина Е.К.Vasilyuk V.B., Boroduleva A.Y., Sobolev P.D., Nikiforova A.G., Mozgovaya V.G., Filon O.V., Zinkovskaya A.V., Ignatiev V.G., Samsonov M.Y., Kozlova I.S., Khanonina E.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1221

Молнупиравир – один из препаратов этиотропной терапии новой коронавирусной инфекции COVID-19, который подтвердил свою клиническую эффективность в терапии пациентов с лёгким и среднетяжёлым течением, в том числе с факторами риска развития тяжёлого течения.

Цель

Цель. Оценка биоэквивалентности воспроизведенного препарата молнупиравира АЛАРИО-ТЛ и оригинального препарата Лагеврио при однократном пероральном применении у здоровых добровольцев.

Материалы и методы

Материалы и методы. Данное исследование биоэквивалентности представляло собой открытое рандомизированное двухпериодное перекрестное исследование. В каждом из двух периодов добровольцы принимали однократно исследуемый или референтный препарат молнупиравира в виде капсул в дозе 200 мг. Отмывочный период между приемами препаратов составил 3 сут. Для определения фармакокинетических параметров и биоэквивалентности оценивали концентрацию основного метаболита молнупиравира N-гидроксицитидина (NHC) в плазме крови добровольцев. Отбор образцов плазмы крови производили в интервале от точки 0 до 16 ч в каждом из периодов исследования. Биоэквивалентность оценивали, сравнивая 90% доверительные интервалы (ДИ) для отношения средних геометрических значений AUC(0–16) и Cmax исследуемого и референтного препаратов с установленными пределами эквивалентности, равными 80,00–125,00%.

Результаты

Результаты. Всего в исследование было включено 28 здоровых добровольцев мужского пола. По результатам проведенного статистического анализа, 90% ДИ для отношения средних геометрических показателей AUC(0–16) и Cmax после приема исследуемого и референтного препаратов составили 96,31% – 113,64% и 91,37% – 114,8%, соответственно. Данные интервалы укладываются в установленные пределы 80,00–125,00%, что подтверждает биоэквивалентность препаратов. При сравнении частоты регистрации отдельных нежелательных явлений не было выявлено достоверных различий после приема исследуемого и референтного препаратов.

Заключение

Заключение. По результатам данного исследования можно заключить, что исследуемый и референтный препараты молнупиравира биоэквивалентны. Кроме того, полученные данные указывают на то, что препараты обладают сходными профилями безопасности.

Molnupiravir is one of the drugs for the etiotropic therapy of a new coronavirus infection COVID-19. It has confirmed its clinical efficacy in the treatment of patients with mild and moderate COVID-19, including those who are at high risk of progressing to severe disease.

The aim of the study was to evaluate bioequivalence of the generic drug molnupiravir ALARIO-TL and the original drug Lagevrio with a single oral administration in healthy volunteers.

Materials and methods

Materials and methods. This bioequivalence study was an open, randomized, two-period crossover study. In each of the two periods, volunteers received a single dose of the test drug, or reference drug molnupiravir, in the form of capsules at the dose of 200 mg. The washout period between the doses was 3 days. To determine pharmacokinetic (PK) parameters and bioequivalence, the concentration the concentration of N-hydrozycytidine (NHC), the main molnupiravir metabolit in the blood plasma of volunteers was evaluated. The blood plasma sampling was carried out in the range from 0 to 16 hours in each of the study periods. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00 – 125.00%.

Results

Results. A total of 28 healthy male volunteers were included in the study. According to the results of the statistical analysis, after the administration of the test and reference drugs, the 90% CIs for the ratio of the geometric means of AUC (0–16) and Cmax were 96.31% – 113.64% and 91.37% – 114.8%, respectively. These intervals fit within the established limits of 80.00–125.00%, which confirms the bioequivalence of the drugs. When comparing the frequency of the individual adverse events registration, no significant differences were found out after the administration of the test and reference drugs.

Conclusion

Conclusion. Based on the results of this study, it can be concluded that the test and reference drugs of molnupiravir are bioequivalent. In addition, the data obtained indicate that the drugs have similar safety profiles.

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