310 Mira Street, Stavropol, Russia, 355017
+7 8652 352524; +7 8652 353229.
+7 8652 352524.
The journal is included into The list of leading scientific periodicals.
The results of a retrospective analysis are presented to determine the coefficients of intraindividual variability and the unification of approaches to the planning and evaluation of bioequivalence studies of HMG-CoA reductase inhibitors. Atorvastatin, simvastatin and lovastatin have demonstrated high intraindividual variability both in the parent compound and in the active metabolite in many studies. The analysis made it possible to formulate recommendations for planning and evaluating atorvastatin, simvastatin, rosuvastatin and lovastatin studies. When choosing the design of studies of atorvastatin, simvastatin and lovastatin, it is necessary to take into account their high intra-individual variability and plan studies either with a standard design and a large sample size of subjects, or research with a replicative design, which will reduce the requirements for the number of subjects. For rosuvastatin, high intraindividual variability was shown only in limited number of studies; therefore, with respect to rosuvastatin preparations, it is sufficient to follow the standard conditions for conducting bioequivalence studies.
1. Davit B. M., Conner D. P., Fabian-Fritsch B., Haidar S. H., Jiang X. [et al.]. Highly Variable Drugs: Observations from Bioequivalence Data Submitted to the FDA for New Generic Drug Applications. AAPS J. 2008;10(1):14856. https://doi.org/10.1208/s12248-008-9015-x
2. Romodanovsky D. P., Dranitsyna M. A., Goryachev D. V., Niyazov R. R., Gavrishina E. V. Design planning and evaluation of the results of bioequivalence studies of highly variable drugs using rosuvastatin as an example. Eksperimentalnaya i klinicheskaya farmakologiya. – Experimental and Clinical Pharmacology. 2015;78(6):19-25. (In Russ.). https://doi.org/10.30906/0869-2092-2015-78-6-19-25
3. Romodanovsky D. P., Goryachev D. V., Solovieva A. P., Eremenko N. N. Principles of Statistical Evaluation of Bioequivalence Studies in the Context of Current Regulatory Requirements and Legal Acts. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya. – The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2018;8(2):92-98. (In Russ.). https://doi.org/10.30895/1991-2919-2018-8-2-92-98
4. Draft Guidance on Atorvastatin Calcium. Product-Specific Guidances for Generic Drug Development FDA. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/psg/ Atorvastatin_tabs_20702_RC5-08.pdf. Accessed March 05, 2020.
5. Khokhlov A. L. Theoretical and practical basis for carrying out studies of reproduced drugs: monograph. Moscow – Yaroslavl – Prague: PhotoLife, 2017. (In Russ.).
6. Draft Guidance on Lovastatin. Product-Specific Guidances for Generic Drug Development FDA. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/psg/%20PSG_021316.pdf Accessed March 05, 2020.
7. Resheniye Soveta Yevrazyskoy ekonomicheskoy komissii ot 3 noyabrya 2016 g. № 85 «Ob utverzhdenii Pravil provedeniya issledovany bioekvivalentnosti lekarstvennykh preparatov v ramkakh Yevrazyskogo ekonomicheskogo soyuza». Available at: https://docs.eaeunion.org/docs/ru-ru/01411942/cncd_21112016_85 Accessed March 05, 2020. (In Russ.).
Keywords: bioequivalence, HMG-CoA reductase inhibitors, atorvastatin, simvastatin, rosuvastatin, lovastatin, high intraindividual variability, study design