Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2025
[Study of drug-drug interactions between Mexidol and thrombolytic drugs].
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Shchulkin A V, Chernykh I V, Abalenikhina Y V, Gatsanoga M V, Gradinar M M, Ananyeva P D, Yakusheva E N
Аннотация
OBJECTIVE: Of the study was to investigate the effect of Mexidol on the fibrinolytic activity of Actilyse, Metalyse and Fortelyzin.
MATERIAL AND METHODS: The study was performed in vitro on blood clots obtained from the blood of wistar rats and healthy donor. The blood clots were incubated with blood plasma for 3 hours at 37 °C to wich Mexidol (0.1, 1, 10 μg/ml), thrombolytics Actilyse (15, 2, 0.5 μg/ml), Metalyse (10, 1, 0.1 μg/ml), Fortelyzin (5, 1.5 and 0.5 μg/ml) or a combination of an antioxidant and thrombolytics were added. To assess the effectiveness of thrombolysis, the % change in blood clotss mass was analyzed, as well as the level of D-dimer in the blood plasma after the end of incubation, which was analyzed by ELISA.
RESULTS: Mexidol in all tested concentrations of 0.1-10 μg/ml did not affect the blood clots mass and D-dimer level. Actilyse in concentrations of 15 and 2 μg/ml caused a decrease in blood clots mass by 27.68±9.45% (p<0.0001) and by 15.72±4.38% (p=0.0011), and a concentration of 15 μg/ml also increased the D-dimer concentration compared to the control by 70.9% (p=0.055). Metalyse at a concentration of 10 μg/ml caused a decrease in blood clots mass by 22.53±2.83% (p<0.0001), at a concentration of 1 μg/ml - by 9.57±2.31% (p<0.0001), at a concentration of 0.1 μg/ml - by 3.76±1.04% (p=0.0115). At a concentration of 10 μg/ml, metalyse also caused an increase in the concentration of D-dimer compared to the control by 37.4% (p=0.0022). The combination of actilyse and metalyse with Mexidol in all tested concentrations did not have a reliable effect on the effectiveness of thrombolytics. Fortelyzin in all concentrations did not cause lysis of blood clots obtained from rat blood, but at a concentration of 5 μg/ml it caused a decrease in the mass of blood clots from human blood by 39.69±15.97% (p<0.001), at a concentration of 1.5 μg/ml - by 33.12±2.48% (p=0.001), and at a concentration of 0.5 μg/ml - by 17.79±5.24% (p=0.078). Mexidol in all tested concentrations did not affect the effectiveness of the thrombolytic.
CONCLUSION: The obtained results indicate that Mexidol does not affect the fibrinolytic activity of Actilyse, Metalyse and Fortelyzin.
MATERIAL AND METHODS: The study was performed in vitro on blood clots obtained from the blood of wistar rats and healthy donor. The blood clots were incubated with blood plasma for 3 hours at 37 °C to wich Mexidol (0.1, 1, 10 μg/ml), thrombolytics Actilyse (15, 2, 0.5 μg/ml), Metalyse (10, 1, 0.1 μg/ml), Fortelyzin (5, 1.5 and 0.5 μg/ml) or a combination of an antioxidant and thrombolytics were added. To assess the effectiveness of thrombolysis, the % change in blood clotss mass was analyzed, as well as the level of D-dimer in the blood plasma after the end of incubation, which was analyzed by ELISA.
RESULTS: Mexidol in all tested concentrations of 0.1-10 μg/ml did not affect the blood clots mass and D-dimer level. Actilyse in concentrations of 15 and 2 μg/ml caused a decrease in blood clots mass by 27.68±9.45% (p<0.0001) and by 15.72±4.38% (p=0.0011), and a concentration of 15 μg/ml also increased the D-dimer concentration compared to the control by 70.9% (p=0.055). Metalyse at a concentration of 10 μg/ml caused a decrease in blood clots mass by 22.53±2.83% (p<0.0001), at a concentration of 1 μg/ml - by 9.57±2.31% (p<0.0001), at a concentration of 0.1 μg/ml - by 3.76±1.04% (p=0.0115). At a concentration of 10 μg/ml, metalyse also caused an increase in the concentration of D-dimer compared to the control by 37.4% (p=0.0022). The combination of actilyse and metalyse with Mexidol in all tested concentrations did not have a reliable effect on the effectiveness of thrombolytics. Fortelyzin in all concentrations did not cause lysis of blood clots obtained from rat blood, but at a concentration of 5 μg/ml it caused a decrease in the mass of blood clots from human blood by 39.69±15.97% (p<0.001), at a concentration of 1.5 μg/ml - by 33.12±2.48% (p=0.001), and at a concentration of 0.5 μg/ml - by 17.79±5.24% (p=0.078). Mexidol in all tested concentrations did not affect the effectiveness of the thrombolytic.
CONCLUSION: The obtained results indicate that Mexidol does not affect the fibrinolytic activity of Actilyse, Metalyse and Fortelyzin.