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Comparative analysis of pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide-based drug for the treatment of obesity

https://doi.org/10.19163/2307-9266-2024-12-3-231-246

Abstract

One of the new classes of drugs for weight loss in overweight and obesity, the safety and efficacy of which have been proven in large-scale studies, are glucagon-like peptide-1 receptor agonists (GLP-1 agonists). Separately, it is worth highlighting the main representative from the GLP-1 agonists class, semaglutide. At a dose of 2.4 mg, this drug demonstrated clinically significant results in terms of the body weight reduction and improvement of cardiometabolic health.

The aim of the work was to evaluate pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of the Velgia® (WRYC12301) at doses of 0.25 mg (0.68 mg/ml) and 2.4 mg (3.2 mg/mL) in comparison with the reference drug Wegovy® (Novo Nordisk A/S, Denmark) at the doses of 0.25 mg (0.68 mg/mL) and 2.4 mg (3.2 mg/mL).

Materials and methods. The study was conducted between March and June 2024. The volunteers (n=60) were randomised into 4 groups (n=15 in each) in a 1:1 ratio to study the semaglutide dosages of 0.25 mg/dose (0.68 mg/mL) in Groups 1, 2 and 2.4 mg/dose (3.2 mg/mL) in Groups 3, 4. The study drug and the reference drug were injected subcutaneously into the anterior abdominal wall. Pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide (solution for subcutaneous administration, JSC Biochemik, Russia) were studied. Some parameters regulating the quality of the active pharmaceutical substance semaglutide, were determined.

Results. The obtained 90% confidence intervals (CIs) for the ratio of Cmax and AUC(0-t) values of the study and reference drugs (Groups 1, 2) at a dose of 0.25 mg (0, 68 mg/mL) were 85.19–114.36% for Cmax and 81.35–112.60% for AUC(0-t), respectively, while for Groups 3, 4, at a dose of 2.4 mg (3.2 mg/mL), Cmax was 83.18–111.3% and AUC(0-t) was 91.70–120.89%, respectively. The obtained 90% CI lies within the established limits, which confirms the bioequivalence of the study and reference drugs. All adverse events registered during the study were of mild severity. According to the results of the immunogenicity parameters analysis, no antibodies to semaglutide were detected in the serum of volunteers.

Conclusion. In the course of the study, the bioequivalence of the study and reference drugs was confirmed. A high safety profile and absence of immunogenicity were demonstrated for the Russian drug Velgia® (WRYC12301, semaglutide, solution for a subcutaneous administration, JSC Biochemik, Russia) in comparison with the reference drug (semaglutide, solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) in doses of 0.25 mg/dose (0.68 mg/mL) and 2.4 mg/dose (3.2 mg/mL).

About the Authors

A. S. Ametov
Russian Medical Academy of Continuing Professional Education
Russian Federation

Doctor of Sciences (Medicine), Professor, Head of the Department of Endocrinology, Head of the UNESCO Network Chair on “Bioethics of Diabetes as a Global Problem”, Russian Medical Academy of Continuous Professional Education; Honoured Scientist of the Russian Federation. 

Bld.1, 2/1, Barrikadnaya Str., Moscow, Russia, 125993



P. A. Bely
Russian University of Medicine
Russian Federation

Doctor of Sciences (Medicine), Senior Laboratory Assistant of Department of Internal Medicine and Gastroenterology, Russian University of Medicine.

4, Dolgorukovskaya Str., Moscow, Russia, 127006



K. Y. Zaslavskaya
National Research Mordovia State University
Russian Federation

Assistant of the Department of Biological and Pharmaceutical Chemistry with the course of organisation and management of pharmacy, National Research Mordovia State University.

68, Bolshevistskaya Str., Saransk, Russia, 430005



E. A. Rogozhina
MIREA, Russian Technological University
Russian Federation

co-researcher of the Department of Biotechnology and Industrial Pharmacy of MIREA, Russian Technological University. 

78, Vernadsky Ave., Moscow, Russia, 119454.



V. S. Shcherbakova
Tver State Medical University
Russian Federation

Candidate of Sciences (Biology), Assistant of the Department of Pharmacology, Tver State Medical University.

4, Sovetskaya Str., Tver, Russia, 170100



Y. G. Kazaishvili
Tver State Medical University
Russian Federation

Candidate of Sciences (Biology), Assistant of the Department of Pharmacology, Tver State Medical University.

4, Sovetskaya Str., Tver, Russia, 170100



A. V. Taganov
Patrice Lumumba Peoples’ Friendship University of Russia (RUDN)
Russian Federation

Doctor of Sciences (Medicine), Professor, Professor of the Department of Dermatology and Venereology with a Course of Cosmetology, Patrice Lumumba Peoples’ Friendship University of Russia (RUDN).

6, Miklukho-Maklay Str., Moscow, Russia, 117198


Competing Interests:

 

 



T. G. Bodrova
Russian University of Medicine
Russian Federation

co-researcher of the K.M. Lakin Scientific and Educational Institute of Pharmacy, Russian University of Medicine.

4, Dolgorukovskaya Str., Moscow, Russia, 127006



E. S. Mishchenko
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Russian Federation

Candidate of Sciences (Pharmacy), Associate Professor of the Department of Toxicological and Analytical Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University. 

11, Kalinin Ave., Pyatigorsk, Russia, 357532



K. N. Koryanova
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Russian Federation

Candidate of Sciences (Pharmacy), Head of the Editorial and Publishing Department, Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University.

11, Kalinin Ave., Pyatigorsk, Russia, 357532



L. I. Shcherbakova
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Russian Federation

Candidate of Sciences (Pharmacy), Associate Professor, Head of the Department of Inorganic, Physical and Colloidal Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University.

11, Kalinin Ave., Pyatigorsk, Russia, 357532



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Review

For citations:


Ametov A.S., Bely P.A., Zaslavskaya K.Y., Rogozhina E.A., Shcherbakova V.S., Kazaishvili Y.G., Taganov A.V., Bodrova T.G., Mishchenko E.S., Koryanova K.N., Shcherbakova L.I. Comparative analysis of pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide-based drug for the treatment of obesity. Pharmacy & Pharmacology. 2024;12(3):231-246. https://doi.org/10.19163/2307-9266-2024-12-3-231-246

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ISSN 2307-9266 (Print)
ISSN 2413-2241 (Online)