Results of bioequivalence studies on the oral contraceptives levonorgestrel+ethinylestradiol, desogestrel+ethinylestradiol and nomegestrol+estradiol in healthy volunteers

Dumanovskaya M.R.

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

Currently, import substitution of medications is one of the priorities of the state policy in the field of healthcare. One of the main criteria for evaluating a generic medication is confirmation of its bioequivalence to the relevant original drug.
Objective: To study the comparative pharmacokinetics and evaluate the bioequivalence of the generic contraceptive drugs PlanyGens in healthy female volunteers after a single oral intake of the drugs on an empty stomach.
Materials and methods: It is an open comparative randomized cross-sectional study with two stages and two subsequent studies. The pharmacokinetic parameters of levonorgestrel, etonogestrel (the active metabolite of desogestrel), nomegestrol, ethinylestradiol and estradiol were determined in the blood plasma of healthy volunteers after a single oral intake of the compared drugs on an empty stomach. The following pharmacological parameters were calculated for the analyzed drugs: AUC0–72, AUC0–∞, Cmax, Tmax, T½, kel, f’, f’’, Cmax/AUC, MRT.
Results: The research presents the results of bioequivalence studies on contraceptives PlanyGens levo, PlanyGens dezo 20, PlanyGens dezo 30, PlanyGens nome produced by “Pharmasyntez-Tyumen” LLC, Russia and relevant original (reference) drugs Microgynon (Bayer Pharma AG, Germany), Mercilon (N.V. Organon, Netherlands), Marvelon (N.V. Organon, Netherlands), and Zoely (N.V. Organon, Netherlands). The 90% confidence intervals for the ratio of the geometric mean AUC0–72 and Cmax parameters lay in the range of 80.00–125.00% in bioequivalence studies of drugs. The safety profiles of all the studied drugs are comparable to the safety profiles of the relevant original drugs.
Conclusion: The bioequivalence of the studied generic contraceptive drugs PlanyGens to the relevant original drugs was confirmed.

Conflict of interest: The author declares no possible conflicts of interest.
Funding: The study was conducted without sponsorship.
Acknowledgements: The author expresses gratitude to Irina A. Proskurina, PhD, Head of the Department No. 2 in the Effectiveness and Safety of Drugs, Scientific Centre for Expert Evaluation of Medicinal Products, for assistance in preparing the article.
For citation: Dumanovskaya M.R. Results of bioequivalence studies on the oral contraceptives levonorgestrel+ethinylestradiol, desogestrel+ethinylestradiol and nomegestrol+estradiol in healthy volunteers. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (11): 180-192 (in Russian)


import substitution
generic drugs
bioequivalence study
combined oral contraceptives
PlanyGens levo
PlanyGens dezo 20
PlanyGens dezo 30
PlanyGens nome


  1. DSM Group. Аналитические обзоры фармацевтического рынка. (дата обращения: 18.10.2023). [DSM Group. Analytical reviews of the pharmaceutical market. (accessed 18.10.2023). (in Russian)].
  2. Григорьева К.Д. Лекарственное импортозамещение-перспективное направление развития российской экономики. Управленческое консультирование. 2018;(5):137-42. [Grigorieva K.D. Drug import replacement is a perspective direction of the development of Russian economy. Administrative Consulting. 2018;(5):137-42. (in Russian)].
  3. Халатян С.Г. Перспективы реализации политики импортозамещения на отечественном фармацевтическом рынке. Молодой ученый. 2016; 25(129): 415-8. [Khalatyan S.G. Prospects for the implementation of the import substitution policy in the domestic pharmaceutical market. Young scientist. 2016; 25(129): 415-8. (in Russian)].
  4. Федеральный Закон от 12.04.2010 № 61-ФЗ «Об обращении лекарственных средств». (дата обращения 18.10.2023). [Federal Law of 12.04.2010 No. 61-FZ "On Circulation of Medicines." (accessed 18.10.2023). (in Russian)].
  5. Аполихина И.А., Тарнаева Л.А., Кондратьева Н.Е. Результаты исследований биоэквивалентности препаратов диеногеста, прогестерона, левоноргестрела+эстрадиол у здоровых добровольцев после однократного приема натощак. Акушерство и гинекология. 2023; 1: 110-21. [Apolikhina I.A., Tarnaeva L.A., Kondratyeva N.E. Results of bioequivalence studies on dienogest, progesterone, and levonorgestrel+estradiol in healthy volunteers after single dose intake during fasting. Obstetrics and Gynecology. 2023; (1): 110-21 (in Russian)].
  6. Quaas P. Kombinierte hormonelle Kontrazeption – welches Präparat für welche Indikation? [Combined hormonal contraception – which pill for which patient?]. Praxis (Bern 1994). 2023;112(4):205-10. German.
  7. Stanczyk F.Z., Winer S.A., Foidart J.M., Archer D.F. Comparison of estrogenic components used for hormonal contraception. Contraception. 2023; 110310.
  8. Сумятина Л.В. Современные гормональные контрацептивы: новые возможности выбора. Проблемы репродукции. 2014;(6): 46‑8. [Sumiatina LV. Modern hormonal contraceptives: new options. Russian Journal of Human Reproduction. 2014;(6):46-8. (in Russian)].
  9. Sitruk-Ware R. Farmacological profile of progestins. Maturitas 2008; 61(1-2): 151-7.
  10. Wiegratz I., Kuh L.H. Metabolic and clinical effects of progestogens. Eur. J. Contracept. Reprod. Health. Care. 2006; 11(3):153-61.
  11. Archer D.F., Maheux R., DeLConte A., O'Brien F.B. Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol (Alesse). North american Levonorgestrel Study Group (NALSG). Am. J. Obstet. Gynecol. 1999; 181(5Pt2): 39-4.
  12. Жуковская И.Г., Хузина Л.Ф. Некоторые аспекты приверженности к комбинированной гормональной контрацепции у молодых женщин. Медицинский Совет. 2022;(16):93-8. [Zhukovskaya I.G., Khuzina L.F. Some aspects of adherence to combined hormonal contraception in young women. Medical Council. 2022;(16):93-8. (in Russian)].
  13. Cherala G., Edelman A., Dorflinger L., Stanczyk F.Z. The elusive minimum threshold concentration of levonorgestrel for contraceptive efficacy. Contraception. 2016; 94(2): 104-8.
  14. Piacenti I, Viscardi M.F., Masciullo L., Sangiuliano C., Scaramuzzino S., Piccioni M.G. et al. Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what's the best choice? Gynecol. Endocrinol. 2021;37(5):471-5.
  15. Бицадзе В.О., Хизроева Д.Х., Солопова А.Г., Кварацхелия М.В., Заболотная Д.Ю., Сяося Ч., Третьякова М.В., Цибизова В.И., Гашимова Н.Р., Григорьева К.Н., Гилева М.А., Шкода А.С., Гри Ж.-К., Макацария А.Д. Как снизить риск венозной тромбоэмболии при приеме комбинированных оральных контрацептивов. Акушерство, Гинекология и Репродукция. 2023; 17(3): 332-42. [Bitsadze V.O., Khizroeva J.Kh., Solopova A.G., Kvaratskheliia M.V., Zabolotnaya D.Yu., Xiaoxia Z., Tretyakova M.V., Tsibizova V.I., Gashimova N.R., Grigoreva K.N., Gileva М.А., Shkoda A.S., Gris J.-K., Makatsariya A.D. How to reduce a risk of venous thromboembolism while taking combined oral contraceptives. Obstetrics, Gynecology and Reproduction. 2023; 17(3):332-42. (in Russian)].
  16. Shamseddin M., De Martino F., Constantin C., Scabia V., Lancelot A.S., Laszlo C. et al. Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation. EMBO Mol. Med. 2021; 13(7): e14314.
  17. Мусина Е.В., Коган И.Ю., Тарасова М.А. Лечебное действие дезогестрела при масталгии у женщин с фиброзно-кистозной болезнью молочных желез. Проблемы репродукции. 2013; (5): 42-6. [Musina E.V., Kogan I.Iu., Tarasova M.A. The therapeutic effect of desogestrel in women with mastalgia and mastopathy. Russian Journal of Human Reproduction. 2013;(5):42-6. (in Russian)].
  18. Burke A. Nomegestrol acetate-17b-estradiol for oral contraception. Patient Prefer. Adherence. 2013;7: 607-19.
  19. Ruan X., Seeger H., Mueck A.O. The pharmacology of nomegestrol acetate. Maturitas. 2012; 71(4): 345-53.
  20. Ebede T.L., Arch E.L., Berson D. Hormonal treatment of acne in women. J. Clin. Aesthet. Dermatol. 2009;2(12):16-22.
  21. Mueck A.O., Sitruk-Ware R. Nomegestrol acetate, a novel progestogen for oral contraception. Steroids. 2011;76(6):531-9. steroids.2011.02.002.
  22. Совет Евразийской экономической комиссии. Решение от 3 ноября 2016 г. N 79 «Об утверждении Правил надлежащей клинической практики Евразийского экономического союза». [Council of the Eurasian Economic Commission. Decision of November 3, 2016 N 79 "On the approval of the Rules of Good Clinical Practice of the Eurasian Economic Union" (in Russian)].
  23. Министерство здравоохранения Российской Федерации. Приказ от 1 апреля 2016 г. N 200н «Об утверждении Правил надлежащей клинической практики». [Ministry of Health of the Russian Federation. Order No. 200n of April 1, 2016 "On Approval of Good Clinical Practice Rules." (in Russian)].
  24. Миронов А.Н., Кукес В.Г., Петров В.И., Кузнецов А.Л., Горячев Д.В., Ниязов Р.Р., Прокофьев А.Б., Недогода С.В., Фролов М.Ю., Шнайдер А. Изучение биоэквивалентности воспроизведенных лекарственных средств. В кн.: Руководство по экспертизе лекарственных средств. т. 1. М.: Гриф и К; 2014: 174-216. [Mironov A.N., Kukes V.G., Petrov V.I., Kuznetsov A.L., Goryachev D.V., Niyazov R.R., Prokofiev A.B., Nedogoda S.V., Frolov M.Yu., Schneider A. Study of bioequivalence of reproduced drugs. In: Guidelines for the examination of medicinal products. vol. 1. Moscow: Grif and K; 2014:174-216. (in Russian)].
  25. Министерство здравоохранения и социального развития Российской Федерации, Федеральная служба по надзору в сфере здравоохранения и социального развития, Федеральное государственное учреждение «Научный центр экспертизы средств медицинского применения». Оценка биоэквивалентности лекарственных средств. Методические указания. М.; 2008. [Ministry of Health and Social Development of the Russian Federation, Federal Service for Surveillance in Healthcare and Social Development, Federal State Institution "Scientific Center for Expertise of Medicinal Products". Evaluation of bioequivalence of drugs. Methodical instructions. Moscow; 2008. (in Russian)].
  26. Правила проведения исследований биоэквивалентности лекарственных препаратов в рамках Евразийского экономического союза (Решение Совета Евразийской экономической комиссии от 3 ноября 2016 г. No 85). [Rules for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union (Decision of the Council of the Eurasian Economic Commission of November 3, 2016 No. 85). (in Russian)].

Received 23.10.2023

Accepted 14.11.2023

About the Authors

Madina R. Dumanovskaya, PhD, Researcher at the Department of Gynecological Endocrinology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia,,,
117997, Russia, Moscow, Ac. Oparin str., 4.

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