Results of bioequivalence studies on dienogest, progesterone, and levonorgestrel+estradiol in healthy volunteers after single dose intake during fasting

DOI

https://dx.doi.org/10.18565/aig.2022.304

Apolikhina I.A., Tarnaeva L.A., Kondratyeva N.E.
1) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia; 3) Pharmasyntez JSC, Moscow, Russia

The paper presents the results of three bioequivalence studies on DlyaZhens metri (dienogest), DlyaZhens pro (progesterone), DlyaZhens klimo (levonorgestrel + estradiol) manufactured by the “Farmasintez-Tyumen” LLC, Russia, and their corresponding original (reference) drugs Visanne (Bayer Pharma AG, Germany), Utrogestan (Besen Healthcare SA, Belgium), and Klimonorm (Jenapharm GmbH & Co. KG, Germany). The bioequivalence studies determined the pharmacokinetic parameters of dienogest, progesterone, and levonorgestrel + estradiol in the plasma of healthy volunteers after single oral dose intake of the compared drugs during fasting according to a 2-stage open-label randomized crossover regimen for dienogest and levonorgestrel + estradiol and according to 4-stage one for progesterone. The plasma concentration of the active ingredients of the drugs was analyzed by a highly sensitive and selective bioanalytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The following pharmacological parameters (AUC0-t, AUC0-∞, AUC0-72, AUCresid, AUCresid%, Cmax, TCmax, T½, kel, f’, Cmax/AUC, and MRT) were calculated for the drugs analyzed. The 90% confidence intervals for the ratios of the geometric mean values of AUC0-t and Cmax were in the range from 80.00 to 125.00% in the bioequivalence studies of dienogest, progesterone, and levonorgestrel + estradiol.
Conclusion: The findings have led to the conclusions about the bioequivalence of the test and reference drugs, such as dienogest, progesterone, and levonorgestrel + estradiol. The safety profiles of the compared drugs were comparable.

Authors’ contributions: Apolikhina I.A. – development of the general concept of the article, literature search, manuscript writing, editing; Tarnayeva L.A. – literature search, text writing; Kondratyeva N.E. – research developer.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has not been sponsored.
Acknowledgement: The authors express their gratitude to Irina A. Proskurina, Can. Med. Sci., Head of the Department Two for Drug Efficacy and Safety, Center for Examination and Control of Ready-Made Drugs, Research Center for Examination of Medicinal Products, Ministry of Health of Russia, for assistance in preparing the article.
For citation: 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.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; 1: 110-121 (in Russian)
https://dx.doi.org/10.18565/aig.2022.304

bioequivalence

pharmacokinetic parameters

dienogest

progesterone

levonorgestrel + estradiol

DlyaZhens metri

DlyaZhens pro

DlyaZhens klimo

Full text (in Russian)

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Received 08.12.2022

Accepted 27.01.2023

Inna A. Apolikhina, Dr. Med. Sci., Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Professor at the Department of Obstetrics, Gynecology, Perinatology and Reproductology of the Institute of Professional Education, I.M. Sechenov 1st Moscow State Medical University, Ministry of Health of Russia (Sechenov University), i_apolikhina@oparina4.ru,
117997, Russia, Moscow, Ac. Oparin str., 4.
Liana A. Tarnaeva, resident, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,
+7(915)112-77-52, li.tarnaeva@ya.ru, 117997, Russia, Moscow, Ac. Oparin str., 4.
Natalya Е. Kondratyeva, PhD, Medical Director, Pharmasintez JSC, +7(916)849-71-32, moscow@pharmasyntez.com,
123100, Russia, Moscow, Presnenskaya nab., 12, Federation Tower (West), 42nd floor.

Results of bioequivalence studies on dienogest, progesterone, and levonorgestrel+estradiol in healthy volunteers after single dose intake during fasting

Apolikhina I.A., Tarnaeva L.A., Kondratyeva N.E.

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