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2 . 2022

Pharmacokinetic assessment of Trombital and Trombital Forte: results of two randomized crossover bioequivalence study

Abstract

Aim 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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CHIEF EDITOR
CHIEF EDITOR
Andrey G. Obrezan
MD, Professor, Head of the Hospital Therapy Department of the Saint Petersburg State University, Chief Physician of SOGAZ MEDICINE Clinical Group, St. Petersburg, Russian Federation
Вскрытие
МКК
Medicine today

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