Pharmacy & PharmacologyPharmacy & PharmacologyФармация и фармакология2307-92662413-2241Eco-Vector37529210.19163/2307-9266-2022-10-6-562-572ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИResearch ArticleBioequivalence study of generic molnupiravir in healthy volunteersИсследование биоэквивалентности воспроизведенного препарата молнупиравира у здоровых добровольцевhttps://orcid.org/0000-0003-2503-4402VasilyukVasily B.ВасилюкВасилий Богданович
Russian Federation

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

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

vasilyuk_vb@ecosafety.ruhttps://orcid.org/0000-0003-1074-5551BorodulevaAnna Yu.БородулеваАнна Юрьевна
Russian Federation

Senior Analytical Chemist

старший химик-аналитик

anna.boroduleva@exactelabs.comhttps://orcid.org/0000-0003-3634-596XSobolevPavel D.СоболевПавел Дмитриевич
Russian Federation

Head of the Laboratory of Bioanalytics

заведующий лабораторией биоаналитики

pavel.sobolev@exactelabs.comhttps://orcid.org/0000-0002-5719-0787NikiforovaAiyyna G.НикифороваАйыына Григорьевна
Russian Federation

Head of the Bioanalytics Department

руководитель отдела биоаналитики

aiyyna.nikiforova@exactelabs.comhttps://orcid.org/0000-0002-8934-8884MozgovayaValentina G.МозговаяВалентина Геннадьевна
Russian Federation

Scientific Adviser

научный советник

mozgovay@rpharm.ruhttps://orcid.org/0000-0002-8735-7429FilonOlga V.ФилонОльга Владимировна
Russian Federation

Department Director

директор департамента

ov.filon@rpharm.ruhttps://orcid.org/0000-0002-7028-0496ZinkovskayaAnna V.ЗинковскаяАнна Васильевна
Russian Federation

Head of the Biostatistics Group of the Department of Preclinical and Clinical Development

руководитель группы биостатистики департамента доклинической и клинической разработки

zinkovskaya@rpharm.ruhttps://orcid.org/0000-0003-2818-6583IgnatievVasily G.ИгнатьевВасилий Геннадьевич
Russian Federation

Candidate of Sciences (Medicine), General Director

кандидат медицинских наук, генеральный директор

info@rpharm.ruhttps://orcid.org/0000-0003-2685-1623SamsonovMikhail Yu.СамсоновМихаил Юрьевич
Russian Federation

Candidate of Sciences (Medicine), Associate Professor, Medical Director

кандидат медицинских наук, доцент, медицинский директор

samsonov@rpharm.ruhttps://orcid.org/0000-0002-2536-296XKozlovaIrina S.КозловаИрина Сергеевна
Russian Federation

Medical Writer

медицинский писатель

is.kozlova@rpharm.ruhttps://orcid.org/0000-0001-5848-0869KhanoninaElizaveta K.ХанонинаЕлизавета Константиновна
Russian Federation

Junior Specialist

младший специалист

khanonina@rphapm.ruLimited Liability Company “Eco-Safety Scientific Research Center”Общество с ограниченной ответственностью «Научно-исследовательский центр Эко-безопасность» (ООО «НИЦ Эко-безопасность»)North-Western State Medical University named after I.I. MechnikovФедеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет имени И.И. Мечникова» Министерства здравоохранения Российской ФедерацииLimited Liability Company “Exacte Labs”Общество с ограниченной ответственностью «Экзактэ Лабс»Limited Liability Company “Exacte Labs”,Общество с ограниченной ответственностью «Экзактэ Лабс»Joint-Stock Company “R-Pharm”Акционерное общество «Р-Фарм»Joint-Stock Company “R-Pharm”Акционерное общество «Р-Фарм»0212202210656257202052023Copyright ©; 2022, 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.Copyright ©; 2022, 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.Copyright ©; 2022, Vasilyuk V., Boroduleva A., Sobolev P., Nikiforova A., Mozgovaya V., Filon O., Zinkovskaya A., Ignatiev V., Samsonov M., Kozlova I., Khanonina E.2022Vasilyuk 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.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.Vasilyuk V., Boroduleva A., Sobolev P., Nikiforova A., Mozgovaya V., Filon O., Zinkovskaya A., Ignatiev V., Samsonov M., Kozlova I., Khanonina E.https://creativecommons.org/licenses/by/4.0https://journals.eco-vector.com/2307-9266/article/view/375292

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. 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. 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. 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.

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

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. 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. 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.

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