Study of the efficacy and safety of sequential use of the drugs Mexidol and Mexidol FORTE 250 in the treatment of stroke
Author:
S.M. KARPOV1, M.YU. MOROZOVA2, K.A. MURAVYOV2, I.A. VYSHLOVA1, F.S. KANTEMIROVA3
1Stavropol State Medical University, Stavropol, Russia;
2City Clinical Hospital No. 3, Stavropol, Russia;
3Georgievsky Medical Academy, Simferopol, Russia
Summary:
Objective. To evaluate the effect of Mexidol on the recovery of cognitive functions in patients after ischemic stroke (IS). Material and methods. We examined 70 patients with acute IS, who were randomized into 2 groups by random sampling; The 1st group consisted of patients who, against the background of the main standard therapy for 14 days, received Mexidol intravenously, 500 mg 1 time per day, followed by oral administration of Mexidol FORTE 250, 750 mg per day for 60 days (40 patients; 28 men, 12 women). Group 2 consisted of 30 patients (21 men, 9 women) who received only standard therapy. Results. Baseline scores on the MoCA and MMSE scales did not differ between the two groups. Retesting showed that the improvement on these scales was statistically more significant in the 1st group. The analysis of indicators of the evoked potential P300 confirmed a more pronounced positive trend in the 1st group (p<0.01). Conclusion. The use of sequential therapy with Mexidol is accompanied by a more complete recovery of cognitive functions in patients who have undergone IS. Keywords: stroke, acute cerebrovascular accident, cognitive impairment, Mexidol, Mexidol FORTE 250.
Generic drugs: benefit/risk ratio
This article is in "Library" section.
Author:
Ushkalova E.A.1, Zyryanov S.K.1,2, Gopienko I.A.1
1Peoples' Friendship University of Russia (RUDN University), Moscow;
2City Clinical Hospital Twenty-Four, Moscow Healthcare Department, Moscow, Russia
Antioxidant activity and toxicity of ethylmethylhydroxypyridine succinate and edaravone: comparative in vitro experiment
This article is in "Library" section.
Author:
A.V. SHCHUL’KIN, YU.V. ABALENIKHINA, P.D. EROKHINA, AND E.N. YAKUSHEVA
Ryazan State Medical University, ul. Vysokovoltnaya 9, Ryazan, 390026 Russia
Generic drugs: benefit/risk ratio
Author:
Ushkalova E.A.1, Zyryanov S.K.1,2, Gopienko I.A.1
1Peoples' Friendship University of Russia (RUDN University), Moscow;
2City Clinical Hospital Twenty-Four, Moscow Healthcare Department, Moscow, Russia
Summary:
The review discusses the interchangeability of medications, approaches to the registration of original and generic drugs, and types of their equivalence, as well as problems with generics in clinical practice. Results of pharmacoepidemiological studies, which have been widely carried out recently, speak of insufficient understanding of the impact of generics on remote outcomes of chronic diseases, including mortality. The longterm economic prospects of generic drug administration continue to remain unclear. Among the primary differences between generics and brandname drugs are the differences in active ingredient synthesis methods and the composition of adjuvants and additives. Comparative studies on the therapeutic equivalence of generics with their originals or between themselves are rarely conducted. They are often affected by methodological flaws, which cannot ensure their comparable efficacy and safety. In this regard, automatic replacement of drugs containing the same active ingredient should be avoided without the participation of the attending physician. Keywords: generics; bioequivalence; pharmaceutical equivalence; therapeutic equivalence; interchangeability.
Antioxidant activity and toxicity of ethylmethylhydroxypyridine succinate and edaravone: comparative in vitro experiment
Author:
A.V. SHCHUL’KIN, YU.V. ABALENIKHINA, P.D. EROKHINA, AND E.N. YAKUSHEVA
Ryazan State Medical University, ul. Vysokovoltnaya 9, Ryazan, 390026 Russia
Summary:
The cytotoxic effect and antioxidant activity of ethylmethylhydroxypyridine succinate (EMHPS) and edaravone were compared in a concentration range of 5 – 5000 mM. The cytotoxic effect was assessed on the HEK293 cell line using the MTT test. The oxidative stress (OS) was modeled by incubation of cells with hydrogen peroxide (Н2О2) at a concentration of 5 mM for an exposure duration of 24 h. The antioxidant activity of both substances was analyzed using their effects on the level of carbonyl derivatives of proteins and TBA-reactive products in the lysate of HEK293 cells. EMHPS reduced the viability of cells only at a concentration of 5 mM to 64.46 + 9.17% (p = 0,021), while edaravone was effective at concentrations of 5, 1, and 0.5 mM by reducing the viability of
cells to 44.55 + 7.43% (p = 0,008), 57.11 + 11.79% (p = 0,013), and 67.97 + 28.07% (p = 0,059), respectively. The OS modeling was accompanied by decrease in the viability of cells to 24.50 + 14.14% (p = 0,033). Both EMHPS and edaravone at concentrations of 50 and 100 mM prevented decrease in the cell viability under OS conditions. However, the EMHPS effect at a concentration of 100 mM was stronger by 30.6% ( p = 0.054) than that of edaravone at a similar concentration in reducing the content of carbonyl derivatives of proteins in the cell lysate. At concentrations of 100 and 50 mM, EMHPS decreased the level of TBA-reactive products in the lysate also stronger than did edaravone – by 43.8% ( p = 0.003) and 38.7% ( p = 0.05), respectively. Thus, results of this study show that EMHPS is a less toxic substance and has more pronounced antioxidant properties in comparison to edaravone.
Keywords: ethylmethylhydroxypyridine succinate; edaravone; oxidative stress; hydrogen peroxide; HEK293 cell line; toxicity; viability.
Original and generic drugs: what does the clinician need to know?
Author:
A.V. SHCHULKIN, A.A. FILIMONOVA
Ryazan State Medical University, Ryazan, Russia
Summary:
In the review article modern approaches to testing and registration of generic drugs are discussed. The article presents the history of the formation of the methodology for testing generic drugs and the current legislation of the Russian Federation. The stages of confirmation of equivalence of original and generic drugs are described: pharmaceutical equivalence, bioequivalence and therapeutic equivalence. The methods of assessing bioequivalence — as the main research in the registration of generic drugs — are discussed in detail. Using the example of the original neuroprotector — Mexidol (ethylmethylhydroxypyridine succinate) and its generics, it is described how legislative acts are implemented in practice. It is concluded that not all generic drugs are interchangeable for the original drug. Keywords: original and generics drugs, ethylmethylhydroxypyridine succinate, mexidol.
Original and generic drugs: what does the clinician need to know?
This article is in "Library" section.
Author:
A.V. SHCHULKIN, A.A. FILIMONOVA
Ryazan State Medical University, Ryazan, Russia
Original and generic drugs: what does the clinician need to know?
Author:
A.V. SHCHULKIN, A.A. FILIMONOVA
Ryazan State Medical University, Ryazan, Russia
Summary:
In the review article modern approaches to testing and registration of generic drugs are discussed. The article presents the history of the formation of the methodology for testing generic drugs and the current legislation of the Russian Federation. The stages of confirmation of equivalence of original and generic drugs are described: pharmaceutical equivalence, bioequivalence and therapeutic equivalence. The methods of assessing bioequivalence — as the main research in the registration of generic drugs — are discussed in detail. Using the example of the original neuroprotector — Mexidol (ethylmethylhydroxypyridine succinate) and its generics, it is described how legislative acts are implemented in practice. It is concluded that not all generic drugs are interchangeable for the original drug. Keywords: original and generics drugs, ethylmethylhydroxypyridine succinate, mexidol.
The efficacy and safety study of Mexidol and Mexidol FORTE 250 in patients with chronic cerebral ischemia
Author:
L.A. SHCHEPANKEVICH1,2, YU.A. NIKOLAEV1, E.V. TANEEVA3, M.A. PERVUNINSKAYA1, M.S. SHCHEPANKEVICH1,2
1Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia;
3State Novosibirsk Regional Clinical Hospital, Novosibirsk, Russia
Summary:
Objective. To study the efficacy and safety of sequential MexidoL therapy, administered intravenously (500 mg once a day) for 14 days, followed by taking the oral form Mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days in elderly patients with chronic cerebral ischemia (CCI) on the background of arterial hypertension and atherosclerosis. Material and methods. An open prospective observational study included 60 patients with an established diagnosis (CCI), confirmed by the results of neuroimaging. All patients were examined with an assessment of neuropsychological status (MoCA test), severity of asthenia (scale MFI-20), emotional state (Hamilton anxiety and depression scale), motor functions (formalized clinical scale for assessing motor activity of elderly Tinetti). The effectiveness of the therapy was evaluated according to the quality of life questionnaire (SF-36). Results. The results of the study showed the high efficiency and safety of sequential therapy with Mexidol in relation to the relief of asthenic and emotional disorders, improving the state of cognitive functions, improving the quality of life of patients. The maximum effect occurred after the end of the full course of therapy. High adherence of patients to the therapy, low frequency of adverse events are shown. Conclusion. Sequential use of intravenous administration of Mexidol followed by oral administration of Mexidol FORTE 250 is an effective and safe way to treat patients with CCI. Keywords: chronic cerebrovascular disease, arterial hypertension, atherosclerosis, ethylmethylhydroxypyridine succinate, mexidol, mexidol forte 250, cognitive impairment.
Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO)
Author:
A.I. FEDIN1, V.V. ZAKHAROV2, M.M. TANASHYAN3, E.I. CHUKANOVA1, E.N. MADZHIDOVA4, L.A. SHCHEPANKEVICH5,6, O.D. OSTROUMOVA7
1Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia;
2Sechenov First Moscow Medical University (Sechenov University), Moscow, Russia;
3Scientific Center of Neurology, Moscow, Russia;
4Tashkent Pediatric Medical Institute, Tashkent, Republic of Uzbekistan;
5Novosibirsk State Medical University, Novosibirsk, Russia;
6Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Russia;
7Russian Medical Academy of Continuous Professional Education, Moscow, Russia
Summary:
Objective. To assess the efficacy and safety of sequential therapy with Mexidol solution for intravenous and intramuscular administration, 50 mg/ml and Mexidol FORTE 250 film-coated tablets, 250 mg in patients with chronic brain ischemia (CBI). Material and methods. An international multicenter, randomized, double-blind, placebo-controlled trial, conducted in 15 clinical centers located in Russian Federation and Republic of Uzbekistan, included 318 patients with CBI aged 40 to 90 years. The patients were randomized into 2 groups, the patients of the 1-st group received Mexidol intravenously 500 mg once daily for 14 days, followed by Mexidol FORTE 250 — 250 mg 3 times a day orally for 60 days; patients of the 2-nd group received a placebo in a similar mode. The primary endpoint was the mean value of difference by MoCA scale at the point of completing the therapy comparing to initial value. Results. According to the results of the assessment of the primary endpoint, statistically significant changes in the MoCA scores at the stage of completion of study were revealed when comparing the dynamics between the 1-st and 2-nd groups (p<0.000001). The lower limit of the 95% confidence interval for the difference in the average of the main efficacy endpoint between the 1-st and 2-nd groups was 1.51, which allows to state a higher efficacy of the use of Mexidol. According to the estimates of secondary endpoints, a statistically significant advantage over placebo at the last visit achieved while evaluation by the following scales and tests: digit symbol substitution test, MFI-20 asthenia assessment scale, Beck anxiety scale, Vane questionnaire, Tinetti scale, SF-36 questionnaire (mental component of health), CGI scale. The comparable nature of the safety profile of Mexidol and Placebo was established. Conclusion. The validity and expediency of the use of Mexidol and Mexidol FORTE 250 in the treatment of patients with CBI has been demonstrated. Keywords: chronic brain ischemia, cognitive impairment, neuropsychological testing, ethylmethylhydroxypyridine succinate, Mexidol, Mexidol FORTE 250, treatment of CBI, MEMO trial.