Bioequivalence study of Rosuvastatin in healthy volunteers after a single dose on an empty stomach

Aim . To assess comparative pharmacokinetics and establish bioequivalence of film-coated Rosuvastatin 20 mg (OOO NTFF "POLYSAN", Russia) (T) and film-coated Crestor® 20 mg (AstraZeneca UK Limited, UK) (R) after a single dose of 20 mg on an empty stomach in healthy volunteers, as well as to study their safety and tolerability. Material and methods . This open-label, randomized, crossover, two-period study of comparative pharmacokinetics and bioequivalence of T and R following a single dose in the fasted state was conducted in 46 healthy volunteers at a single center. After randomization, volunteers in each Study Period received a single 20 mg rosuvastatin dose in a different sequence (TR or RT). Periods I and II were separated by a 14-day washout period. Plasma rosuvastatin concentrations were determined by high-liquid chromatography–mass spectrometry. Following pharmacokinetic parameters were calculated: area under the concentration-time from 0 to 72 h (AUC 0 - t ) and the maximum concentration (C max ). The drugs were considered bioequivalent if the 90% confidence intervals (CI) of the T/R geometric mean ratios for C max and AUC 0 - t were in the range of 80-125%. Safety assessment included analysis of vital signs, physical examination, laboratory tests, 12-lead electrocardiography (ECG), and registration of adverse events (AEs) during the study. Results . Of the 46 randomized volunteers, 44 comprised the safety population. Forty two participants completed the study without significant protocol deviations and comprised the population for pharmacokinetic, statistical analysis and bioequivalence. The values of pharmacokinetic parameters T and R were comparable. The 90% CIs for C max and AUC 0 - t were within the acceptable bioequivalence range of 80,00-125,00% as follows: 91,71-107,41% and 91,58-115,83%, respectively. A total of 2 AEs were recorded in 1 participant after receiving the reference drug. The frequency of AEs did not differ between the groups. No clinically significant deviations in vital signs, physical examinations, laboratory tests, or ECG data were observed in either group during the study. Conclusion . T and R were considered bioequivalent and demonstrated similar safety profiles.