Pharmacokinetic assessment of Trombital and Trombital Forte: results of two randomized crossover bioequivalence study
AbstractAim – evaluation of the pharmacokinetics (PK), bioequivalence and safety profile of the Trombital and Trombital Forte comparing with that of Cardiomagnyl®.
Material and methods. Each of these two studies was a randomized, open, single-dose, two-arm and two-period crossover Phase I study. In the first study, subjects were randomized evenly to a single dose of Trombital 2 tablets (75 mg acetylsalicylic acid + 15.2 mg magnesium hydroxid) or reference drug (150 mg acetylsalicylic acid + 30.39 mg magnesium hydroxid). In the second study, subjects received either single dose of Trombital Forte (150 mg acetylsalicylic acid + 30.39 mg magnesium hydroxid) or reference drug. The primary PK endpoints were area under the curve (AUC), peak concentration (Cmax) and Cmax/AUC. Bioequivalence was determined by assessing whether the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) of Trombital and Trombital Forte to reference drug fell within predefined margins of 80–125%. Incidence of adverse events was similar (p>0.05) between the two groups.
Results. Mean values of primary PK parameters were similar (p>0.05) between Trombital, Trombital Forte and reference drug. For acetylsalicylic acid, the 90% CIs for primary PK endpoints’ GMR of Trombital AUC 0–24 to reference drug AUC 0–24 ranged between 90–42% and 107.98%; for salicylic acid, the 90% CIs were 89.90% to 110.66%; for Cmax – 94.97% to 115.18% and 88.71% to 105.98%, respectively; for Cmax/AUC 0–24 and Cmax/AUC 0–∞ – 96.27% to 116.37% and 92.24% to 102.46% respectively. In the second study, for acetylsalicylic acid, the 90% CIs for primary PK endpoints’ GMR of Trombital Forte AUC 0–24 to reference drug AUC 0–24 ranged between 89.33% and 109.74%; for salicylic acid, the 90% CIs were 88.18% to 108.01%; for Cmax 91.14% to 110.88% and 96.06% to 113.08%, respectively; for Cmax/AUC 0–24 and Cmax/AUC 0–∞ 90.12% to 114.38% and 98.90% to 115.33%, respectively. All 90% CIs were within bioequivalence margins of 80–125%. Incidence of AEs was similar (p>0.05) between the two groups.
Conclusion. Trombital and Trombital Forte and reference drug were bioequivalent The PK and safety assessments were similar (p>0.05) between the two formulations in healthy subjects.
Keywords:Trombital; Trombital Forte; Cardiomagnyl®; platelet; bioequivalence
Funding. The study was conducted with the sponsorship of JSC “OTISIPHARM”.
Conflict of interest. The authors declare no conflict of interest.
For citation: Dzhioeva O.N., Karaeva E.N., Kukes I.V., Soloveva E.Yu. Pharmacokinetic assessment of Trombital and Trombital Forte: results of two randomized, crossover, bioequivalence study // Kardiologiya: novosti, mneniya, obuchenie [Cardiology: News, Opinions, Training]. 2022; 10 (2): 28–37. DOI: https://doi.org/10.33029/2309-1908-2022-10-12-28-37 (in Russian)
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