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Elena V Parfenyuk - One of the best experts on this subject based on the ideXlab platform.
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Design of silica carrier for controlled release of Molsidomine: effect of preparation methods of silica matrixes and their composites with Molsidomine on the drug release kinetics in vitro.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2014Co-Authors: Elena V Parfenyuk, Ekaterina S. DolininaAbstract:Abstract Biodegradable, controlled-release carrier materials with non-toxic degradation products are very valuable for delivery of cardiovascular drugs. This study is a part of development of novel form of vasodilator Molsidomine to improve pharmacokinetic and consumer properties of the drug. It focuses on the effect of preparation methods of the drug–silica composites on their release kinetics. Phenyl modified silica materials prepared by different ways were studied as potential carriers for Molsidomine. The composites of Molsidomine with the modified silica were synthesized via one-step sol–gel route and adsorption. The drug was adsorbed onto the phenyl modified silica prepared by co-condensation and grafting. Furthermore, the one-step sol–gel derived composites were prepared at pH 4.4 (the isoelectric point of the drug) and pH 6.3 (the zero point of charge of the silica). In vitro release kinetics of Molsidomine from the synthesized composites in simulated gastric (pH 1.6) and simulated blood (pH 7.4) media was studied. Our findings demonstrate that the release of the drug can be controlled by manipulating the synthesis ways and changing the sol–gel pH. The comparative analysis of Molsidomine release profiles from the composites prepared by one-step sol–gel synthesis at different pH and adsorption allows to reveal perspective composites which exhibit sustained release of Molsidomine for about 36 h in acidic medium close to the zero order release kinetics.
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comparative study of adsorption capacity of mesoporous silica materials for Molsidomine effects of functionalizing and solution ph
Materials Science and Engineering: C, 2014Co-Authors: N A Alyoshina, A V Agafonov, Elena V ParfenyukAbstract:Abstract Adsorption capacities of mesoporous silica materials having various surface functional groups (hydroxyl, phenyl, mercaptopropyl, aminopropyl) at pH values of 4.8, 7.4, and 8.0 were studied. It was found that the maximum amount of adsorbed Molsidomine is affected by method of preparation of the silica materials, chemistry of their surfaces and solution pH from where adsorption is carried out. The effects were explained by different states of the adsorbents and Molsidomine in solution at the studied pH. The most efficient adsorption of Molsidomine is observed onto phenyl modified silica prepared by grafting at pH 4.8. Aminopropyl modified silica adsorbs the lowest amount of Molsidomine and the adsorption was observed only at pH 7.4. Interactions responsible for the adsorption were elucidated by spectroscopic studies.
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The effects of surface chemistry of mesoporous silica materials and solution pH on kinetics of Molsidomine adsorption
Journal of Solid State Chemistry, 2014Co-Authors: Ekaterina S. Dolinina, Elena V ParfenyukAbstract:Abstract Adsorption kinetics of Molsidomine on mesoporous silica material (UMS), the phenyl- (PhMS) and mercaptopropyl-functionalized (MMS) derivatives from solution with different pH and 298 K was studied. The adsorption kinetics was found to follow the pseudo-second-order kinetic model for all studied silica materials and pH. Effects of surface functional groups and pH on adsorption efficiency and kinetic adsorption parameters were investigated. At all studied pH, the highest Molsidomine amount is adsorbed on PhMS due to π–π interactions and hydrogen bonding between surface groups of PhMS and Molsidomine molecules. An increase of pH results in a decrease of the amounts of adsorbed Molsidomine onto the silica materials. Furthermore, the highest adsorption rate kinetically evaluated using a pseudo-second-order model, is observed onto UMS and it strongly depends on pH. The mechanism of the adsorption process was determined from the intraparticle diffusion and Boyd kinetic film–diffusion models. The results showed that the Molsidomine adsorption on the silica materials is controlled by film diffusion. Effect of pH on the diffusion parameters is discussed.
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Functionalized mesoporous silica materials for Molsidomine adsorption: Thermodynamic study
Journal of Solid State Chemistry, 2013Co-Authors: N A Alyoshina, Elena V ParfenyukAbstract:Abstract A series of unmodified and organically modified mesoporous silica materials was prepared. The unmodified mesoporous silica was synthesized via sol–gel synthesis in the presence of d -glucose as pore-forming agent. The functionalized by phenyl, aminopropyl and mercaptopropyl groups silica materials were prepared via grafting. The fabricated adsorbent materials were characterized by Fourier transform infrared spectroscopy (FTIR) analysis, N 2 adsorption/desorption and elemental analysis methods. Then their adsorption properties for mesoionic dug Molsidomine were investigated at 290–313 K and physiological pH value. Thermodynamic parameters of Molsidomine adsorption on the synthesized materials have been calculated. The obtained results showed that the adsorption process of Molsidomine on the phenyl modified silica is the most quantitatively and energetically favorable. The unmodified and mercaptopropyl modified silica materials exhibit significantly higher adsorption capacities and energies for Molsidomine than the aminopropyl modified sample. The effects are discussed from the viewpoint of nature of specific interactions responsible for the adsorption.
Joseph Géczy - One of the best experts on this subject based on the ideXlab platform.
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Clinical pharmacokinetics of once-daily Molsidomine
American Journal of Drug Delivery, 2004Co-Authors: André Herchuelz, Fabienne Carreer-bruhwyler, Jacques Crommen, Patrice Chiap, Philippe Hubert, Roger Messin, Claude Dubois, Jean-pierre Famaey, Joseph GéczyAbstract:Background Molsidomine is a direct nitric oxide donor routinely used in the oral treatment of stable angina pectoris. It was initially available as 4mg immediate-release tablets to be taken three to four times a day. New galenic formulations have been developed: prolonged-release Molsidomine 8mg to be administered twice daily and, more recently, prolonged-release Molsidomine 16mg to be taken once daily, the latter being based on the patented and US FDA-approved Geomatrix® technology. Objectives This study has four objectives: (i) to compare and differentiate the pharmacokinetics of the different Molsidomine formulations after single- and repeated-dose administrations; (ii) to put the new formulations in perspective with the literature and the critical minimal efficacy plasma Molsidomine concentration of 5 µg/L; (iii) to demonstrate a possible bioequivalence between 8mg twice-daily and 16mg once-daily tablets when used at their recommended therapeutic dosage regimen; and (iv) to assess the effect of food and age on the absorption, distribution, and elimination of the new once-daily formulation. Methods Different dosages of various formulations of Molsidomine were administered to young and elderly healthy volunteers and plasma concentrations of Molsidomine and its active metabolite, linsidomine (SIN-1), were determined. Plasma concentrations were determined using solid-phase extraction and enrichment of the extracts on a short column followed by elution of the analytes by liquid Chromatographic mobile phase and ultraviolet detection. Results Compared with previous formulations, Molsidomine 16mg once daily showed an increased time to maximum plasma concentration and a tendency to a lower mean maximum plasma concentration. Plasma Molsidomine concentrations were always above the efficacy threshold of 5 µg/L during the whole 24-hour cycle and the concentration at trough was still in the therapeutic range. No drug accumulation was observed after repeated administration. Bioequivalence between Molsidomine 16mg once daily and Molsidomine 8mg twice daily could not be demonstrated after 1 and 5 days of treatment, the relative bioavailability being significantly larger with the latter regimen. Pharmacokinetics of Molsidomine 16mg once daily was not significantly affected by either concomitant food ingestion (no major effect of a high-fat meal) or aging (no major difference between young and elderly healthy volunteers). Conclusions Molsidomine 16mg once daily allowed the maintenance of a therapeutically active plasma concentration over 24 hours after single or repeated oral administration. The bioavailability of Molsidomine from the once-daily preparation is apparently not affected by concomitant administration of food or age of the recipient.
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clinical pharmacokinetics of once daily Molsidomine from immediate release to prolonged release once daily formulations
American Journal of Drug Delivery, 2004Co-Authors: André Herchuelz, Jacques Crommen, Patrice Chiap, Philippe Hubert, Claude Dubois, Jean-pierre Famaey, R Messin, Fabienne Carreerbruhwyler, Joseph GéczyAbstract:Background Molsidomine is a direct nitric oxide donor routinely used in the oral treatment of stable angina pectoris. It was initially available as 4mg immediate-release tablets to be taken three to four times a day. New galenic formulations have been developed: prolonged-release Molsidomine 8mg to be administered twice daily and, more recently, prolonged-release Molsidomine 16mg to be taken once daily, the latter being based on the patented and US FDA-approved Geomatrix® technology.
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A pilot double-blind randomized placebo-controlled study of Molsidomine 16 mg once-a-day in patients suffering from stable angina pectoris: correlation between efficacy and over time plasma concentrations
European Journal of Clinical Pharmacology, 2003Co-Authors: Roger Messin, Fabienne Carreer-bruhwyler, Jacques Crommen, Patrice Chiap, Philippe Hubert, Claude Dubois, Jean-pierre Famaey, Tamas Fenyvesi, Joseph GéczyAbstract:Objectives A new once-a-day (o.a.d.) formulation of Molsidomine (16 mg) was evaluated in patients with stable angina pectoris. The aims were to characterize its pharmacokinetics after a single dose, to demonstrate its clinical efficacy and safety versus placebo and to investigate correlations between pharmacokinetics and pharmacodynamics. Methods Forty-two patients were recruited in a double-blind, crossover, randomized placebo-controlled trial. The pharmacokinetics of Molsidomine and SIN-1, its active metabolite, were determined at specific time points (3, 6, 10, 14, 18, 22 and 24 h) after the administration of a single dose of Molsidomine 16 mg o.a.d. in all patients distributed into seven groups. Twenty-eight of these 42 patients showed a positive baseline cycloergometric exercise test response during the run-in placebo period and were used to compare the efficacy of Molsidomine to placebo. Relationships between plasma concentration in Molsidomine or SIN-1 and ischemic threshold were assessed in 16 of the 28 patients with a positive exercise test at baseline. Indeed, the censored variable ischemia-limited tolerance to exercise could not be evaluated in those patients who did not show exercise-induced ischemia anymore under Molsidomine 16 mg o.a.d. Pharmacokinetic–pharmacodynamic relationships were evaluated using regression models and correlation coefficients. Results The highest average concentration in Molsidomine and SIN-1 occurred after 6 h, then a plateau of 15–20 ng/ml Molsidomine and 0.8–3.0 ng/ml SIN-1 was maintained for at least 8 h and the mean residual Molsidomine concentration 24 h post-drug intake was around 8 ng/ml, still in the effective range of 5–10 ng/ml. A significant increase in total workload (+52 W min, P =0.009), total exercise time (+32 s, P =0.003) and time to angina (+25 s, P =0.016) was measured with Molsidomine 16 mg o.a.d. relative to placebo. Using linear regression, significant correlation coefficients were determined between Molsidomine plasma concentrations (but not SIN-1) and exercise test improvements (r=0.827, P
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a pilot double blind randomized placebo controlled study of Molsidomine 16 mg once a day in patients suffering from stable angina pectoris correlation between efficacy and over time plasma concentrations
European Journal of Clinical Pharmacology, 2003Co-Authors: R Messin, Jacques Crommen, Patrice Chiap, Philippe Hubert, Claude Dubois, Jean-pierre Famaey, Tamas Fenyvesi, Fabienne Carreerbruhwyler, Joseph GéczyAbstract:A new once-a-day (o.a.d.) formulation of Molsidomine (16 mg) was evaluated in patients with stable angina pectoris. The aims were to characterize its pharmacokinetics after a single dose, to demonstrate its clinical efficacy and safety versus placebo and to investigate correlations between pharmacokinetics and pharmacodynamics. Forty-two patients were recruited in a double-blind, crossover, randomized placebo-controlled trial. The pharmacokinetics of Molsidomine and SIN-1, its active metabolite, were determined at specific time points (3, 6, 10, 14, 18, 22 and 24 h) after the administration of a single dose of Molsidomine 16 mg o.a.d. in all patients distributed into seven groups. Twenty-eight of these 42 patients showed a positive baseline cycloergometric exercise test response during the run-in placebo period and were used to compare the efficacy of Molsidomine to placebo. Relationships between plasma concentration in Molsidomine or SIN-1 and ischemic threshold were assessed in 16 of the 28 patients with a positive exercise test at baseline. Indeed, the censored variable ischemia-limited tolerance to exercise could not be evaluated in those patients who did not show exercise-induced ischemia anymore under Molsidomine 16 mg o.a.d. Pharmacokinetic–pharmacodynamic relationships were evaluated using regression models and correlation coefficients. The highest average concentration in Molsidomine and SIN-1 occurred after 6 h, then a plateau of 15–20 ng/ml Molsidomine and 0.8–3.0 ng/ml SIN-1 was maintained for at least 8 h and the mean residual Molsidomine concentration 24 h post-drug intake was around 8 ng/ml, still in the effective range of 5–10 ng/ml. A significant increase in total workload (+52 W min, P=0.009), total exercise time (+32 s, P=0.003) and time to angina (+25 s, P=0.016) was measured with Molsidomine 16 mg o.a.d. relative to placebo. Using linear regression, significant correlation coefficients were determined between Molsidomine plasma concentrations (but not SIN-1) and exercise test improvements (r=0.827, P<0.001 for the total workload; r=0.772, P<0.001 for the total exercise time; and r=0.566, P=0.028 for the time to 1 mm ST-segment depression). The pharmacokinetics of Molsidomine 16 mg in patients with stable angina pectoris is compatible with a o.a.d. dosage regimen. This o.a.d. formulation is effective and well-tolerated, providing a 24-h therapeutic control of myocardial ischemia. A positive and significant linear relationship between Molsidomine plasma concentration and the increase in exercise tolerance was observed.
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Short- and long-term effects of Molsidomine retard and Molsidomine nonretard on exercise capacity and clinical status in patients with stable angina: a multicenter randomized double-blind crossover placebo-controlled trial.
Journal of cardiovascular pharmacology, 1998Co-Authors: Roger Messin, Youri Karpov, Natalia Baikova, Jacques Bruhwyler, Marie-joëlle Monseu, Corry Guns, Joseph GéczyAbstract:A multicenter, randomized, double-blind, crossover, placebo-controlled study was conducted in 90 isosorbide dinitrate responders showing stable angina to compare the efficacy of Molsidomine retard, 8 mg b.i.d., with that of Molsidomine, 4 mg t.i.d., for 6 weeks. Total work performance (workload x min) was significantly improved, compared with baseline and placebo until 8 and 12 h after Molsidomine and Molsidomine retard administration, respectively. ST-segment depression decreased significantly under the two treatments at 60 W as well as at maximal exercise. The rate-pressure product (heart rate x systolic blood pressure) decreased and increased significantly at submaximal and maximal exercise level, respectively. All these effects remained significant after 6-week treatment, with only the ST segment showing a nonsignificant tendency to improvement at maximal work. The frequency of anginal attacks and of sublingual nitroderivative-tablets consumption decreased significantly with Molsidomine, 4 mg, and Molsidomine retard, 8 mg. However, overall results showed that the latter form reduces myocardial ischemia more efficiently at submaximal exercise level, has a more prolonged effect on exercise tolerance, and maintains it at a somewhat higher level after 6-week treatment.
Roger Messin - One of the best experts on this subject based on the ideXlab platform.
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Comparative Short-Term Effect of Once-Daily Molsidomine on Chronic Angina in General Practitioners’ versus Cardiologists’ Coronary Patient Populations
Advances in Therapy, 2014Co-Authors: Roger MessinAbstract:Introduction The direct nitric oxide donor Molsidomine is commonly used to relieve symptoms in chronic angina thanks to its vasodilatory properties that induce both a reduction in myocardial oxygen demand and an increase in coronary blood flow. The objective of this study was to compare the short-term effect of Molsidomine 16 mg once daily (Coruno^®, Therabel Pharmaceuticals Ltd, Dublin, Ireland) in patients with stable angina previously on Molsidomine 8 mg twice daily, in care of general practitioners (GPs) versus cardiologists. Methods A total of 53 and 80 patients treated by GPs and cardiologists, respectively, took part in this multicenter, open-label clinical trial. Frequency of anginal attacks, short-acting nitroderivative tablets consumption, and subjective clinical status were evaluated, as was tolerability to Molsidomine through the reporting of adverse events (AEs), the recording of vital parameters—resting blood pressure, heart rate, and electrocardiogram—and routine blood analyses. Results Although demographic and clinical characteristics were significantly different in GPs’ compared with cardiologists’ patients, the effect of either the 8 mg or the 16 mg Molsidomine formulation on anginal crises and nitroderivatives consumption was similar in both patient cohorts, with a trend for the 16 mg formulation to be more efficient on symptoms in elderly patients. Subjective assessment of the beneficial effect of Molsidomine 16 versus 8 mg was comparable in GPs’ and cardiologists’ patients independently of age, “no change” being the most often reported item. Self-evaluation of functional capacity in elderly showed on the whole no difference between the two patient cohorts, only magnitude of pace and total score on Molsidomine 16 mg being higher in cardiologists’ compared with GPs’ patients, and total score in cardiologists’ patients higher on Molsidomine 16 mg compared with 8 mg. Incidences of AEs and drug-related AEs, as well as proportions of patients reporting such AEs, were similar between GPs’ and cardiologists’ patient cohorts as between Molsidomine 8 and 16 mg formulations. Molsidomine 16 mg once daily had no clinically significant effect on blood pressure, heart rate, electrocardiogram or blood parameters, and compliance with treatment was excellent in whatever patient cohort. Conclusion Despite significant demographic and clinical differences between patients in care of GPs and cardiologists, Molsidomine was equally efficient in these two patient cohorts, with a trend towards less anginal attacks in the elderly when treated with the 16 mg compared with the 8 mg formulation. Compliance and tolerability to the drug were excellent in both patient cohorts.
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Clinical pharmacokinetics of once-daily Molsidomine
American Journal of Drug Delivery, 2004Co-Authors: André Herchuelz, Fabienne Carreer-bruhwyler, Jacques Crommen, Patrice Chiap, Philippe Hubert, Roger Messin, Claude Dubois, Jean-pierre Famaey, Joseph GéczyAbstract:Background Molsidomine is a direct nitric oxide donor routinely used in the oral treatment of stable angina pectoris. It was initially available as 4mg immediate-release tablets to be taken three to four times a day. New galenic formulations have been developed: prolonged-release Molsidomine 8mg to be administered twice daily and, more recently, prolonged-release Molsidomine 16mg to be taken once daily, the latter being based on the patented and US FDA-approved Geomatrix® technology. Objectives This study has four objectives: (i) to compare and differentiate the pharmacokinetics of the different Molsidomine formulations after single- and repeated-dose administrations; (ii) to put the new formulations in perspective with the literature and the critical minimal efficacy plasma Molsidomine concentration of 5 µg/L; (iii) to demonstrate a possible bioequivalence between 8mg twice-daily and 16mg once-daily tablets when used at their recommended therapeutic dosage regimen; and (iv) to assess the effect of food and age on the absorption, distribution, and elimination of the new once-daily formulation. Methods Different dosages of various formulations of Molsidomine were administered to young and elderly healthy volunteers and plasma concentrations of Molsidomine and its active metabolite, linsidomine (SIN-1), were determined. Plasma concentrations were determined using solid-phase extraction and enrichment of the extracts on a short column followed by elution of the analytes by liquid Chromatographic mobile phase and ultraviolet detection. Results Compared with previous formulations, Molsidomine 16mg once daily showed an increased time to maximum plasma concentration and a tendency to a lower mean maximum plasma concentration. Plasma Molsidomine concentrations were always above the efficacy threshold of 5 µg/L during the whole 24-hour cycle and the concentration at trough was still in the therapeutic range. No drug accumulation was observed after repeated administration. Bioequivalence between Molsidomine 16mg once daily and Molsidomine 8mg twice daily could not be demonstrated after 1 and 5 days of treatment, the relative bioavailability being significantly larger with the latter regimen. Pharmacokinetics of Molsidomine 16mg once daily was not significantly affected by either concomitant food ingestion (no major effect of a high-fat meal) or aging (no major difference between young and elderly healthy volunteers). Conclusions Molsidomine 16mg once daily allowed the maintenance of a therapeutically active plasma concentration over 24 hours after single or repeated oral administration. The bioavailability of Molsidomine from the once-daily preparation is apparently not affected by concomitant administration of food or age of the recipient.
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A pilot double-blind randomized placebo-controlled study of Molsidomine 16 mg once-a-day in patients suffering from stable angina pectoris: correlation between efficacy and over time plasma concentrations
European Journal of Clinical Pharmacology, 2003Co-Authors: Roger Messin, Fabienne Carreer-bruhwyler, Jacques Crommen, Patrice Chiap, Philippe Hubert, Claude Dubois, Jean-pierre Famaey, Tamas Fenyvesi, Joseph GéczyAbstract:Objectives A new once-a-day (o.a.d.) formulation of Molsidomine (16 mg) was evaluated in patients with stable angina pectoris. The aims were to characterize its pharmacokinetics after a single dose, to demonstrate its clinical efficacy and safety versus placebo and to investigate correlations between pharmacokinetics and pharmacodynamics. Methods Forty-two patients were recruited in a double-blind, crossover, randomized placebo-controlled trial. The pharmacokinetics of Molsidomine and SIN-1, its active metabolite, were determined at specific time points (3, 6, 10, 14, 18, 22 and 24 h) after the administration of a single dose of Molsidomine 16 mg o.a.d. in all patients distributed into seven groups. Twenty-eight of these 42 patients showed a positive baseline cycloergometric exercise test response during the run-in placebo period and were used to compare the efficacy of Molsidomine to placebo. Relationships between plasma concentration in Molsidomine or SIN-1 and ischemic threshold were assessed in 16 of the 28 patients with a positive exercise test at baseline. Indeed, the censored variable ischemia-limited tolerance to exercise could not be evaluated in those patients who did not show exercise-induced ischemia anymore under Molsidomine 16 mg o.a.d. Pharmacokinetic–pharmacodynamic relationships were evaluated using regression models and correlation coefficients. Results The highest average concentration in Molsidomine and SIN-1 occurred after 6 h, then a plateau of 15–20 ng/ml Molsidomine and 0.8–3.0 ng/ml SIN-1 was maintained for at least 8 h and the mean residual Molsidomine concentration 24 h post-drug intake was around 8 ng/ml, still in the effective range of 5–10 ng/ml. A significant increase in total workload (+52 W min, P =0.009), total exercise time (+32 s, P =0.003) and time to angina (+25 s, P =0.016) was measured with Molsidomine 16 mg o.a.d. relative to placebo. Using linear regression, significant correlation coefficients were determined between Molsidomine plasma concentrations (but not SIN-1) and exercise test improvements (r=0.827, P
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Short- and long-term effects of Molsidomine retard and Molsidomine nonretard on exercise capacity and clinical status in patients with stable angina: a multicenter randomized double-blind crossover placebo-controlled trial.
Journal of cardiovascular pharmacology, 1998Co-Authors: Roger Messin, Youri Karpov, Natalia Baikova, Jacques Bruhwyler, Marie-joëlle Monseu, Corry Guns, Joseph GéczyAbstract:A multicenter, randomized, double-blind, crossover, placebo-controlled study was conducted in 90 isosorbide dinitrate responders showing stable angina to compare the efficacy of Molsidomine retard, 8 mg b.i.d., with that of Molsidomine, 4 mg t.i.d., for 6 weeks. Total work performance (workload x min) was significantly improved, compared with baseline and placebo until 8 and 12 h after Molsidomine and Molsidomine retard administration, respectively. ST-segment depression decreased significantly under the two treatments at 60 W as well as at maximal exercise. The rate-pressure product (heart rate x systolic blood pressure) decreased and increased significantly at submaximal and maximal exercise level, respectively. All these effects remained significant after 6-week treatment, with only the ST segment showing a nonsignificant tendency to improvement at maximal work. The frequency of anginal attacks and of sublingual nitroderivative-tablets consumption decreased significantly with Molsidomine, 4 mg, and Molsidomine retard, 8 mg. However, overall results showed that the latter form reduces myocardial ischemia more efficiently at submaximal exercise level, has a more prolonged effect on exercise tolerance, and maintains it at a somewhat higher level after 6-week treatment.
R Messin - One of the best experts on this subject based on the ideXlab platform.
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clinical pharmacokinetics of once daily Molsidomine from immediate release to prolonged release once daily formulations
American Journal of Drug Delivery, 2004Co-Authors: André Herchuelz, Jacques Crommen, Patrice Chiap, Philippe Hubert, Claude Dubois, Jean-pierre Famaey, R Messin, Fabienne Carreerbruhwyler, Joseph GéczyAbstract:Background Molsidomine is a direct nitric oxide donor routinely used in the oral treatment of stable angina pectoris. It was initially available as 4mg immediate-release tablets to be taken three to four times a day. New galenic formulations have been developed: prolonged-release Molsidomine 8mg to be administered twice daily and, more recently, prolonged-release Molsidomine 16mg to be taken once daily, the latter being based on the patented and US FDA-approved Geomatrix® technology.
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a pilot double blind randomized placebo controlled study of Molsidomine 16 mg once a day in patients suffering from stable angina pectoris correlation between efficacy and over time plasma concentrations
European Journal of Clinical Pharmacology, 2003Co-Authors: R Messin, Jacques Crommen, Patrice Chiap, Philippe Hubert, Claude Dubois, Jean-pierre Famaey, Tamas Fenyvesi, Fabienne Carreerbruhwyler, Joseph GéczyAbstract:A new once-a-day (o.a.d.) formulation of Molsidomine (16 mg) was evaluated in patients with stable angina pectoris. The aims were to characterize its pharmacokinetics after a single dose, to demonstrate its clinical efficacy and safety versus placebo and to investigate correlations between pharmacokinetics and pharmacodynamics. Forty-two patients were recruited in a double-blind, crossover, randomized placebo-controlled trial. The pharmacokinetics of Molsidomine and SIN-1, its active metabolite, were determined at specific time points (3, 6, 10, 14, 18, 22 and 24 h) after the administration of a single dose of Molsidomine 16 mg o.a.d. in all patients distributed into seven groups. Twenty-eight of these 42 patients showed a positive baseline cycloergometric exercise test response during the run-in placebo period and were used to compare the efficacy of Molsidomine to placebo. Relationships between plasma concentration in Molsidomine or SIN-1 and ischemic threshold were assessed in 16 of the 28 patients with a positive exercise test at baseline. Indeed, the censored variable ischemia-limited tolerance to exercise could not be evaluated in those patients who did not show exercise-induced ischemia anymore under Molsidomine 16 mg o.a.d. Pharmacokinetic–pharmacodynamic relationships were evaluated using regression models and correlation coefficients. The highest average concentration in Molsidomine and SIN-1 occurred after 6 h, then a plateau of 15–20 ng/ml Molsidomine and 0.8–3.0 ng/ml SIN-1 was maintained for at least 8 h and the mean residual Molsidomine concentration 24 h post-drug intake was around 8 ng/ml, still in the effective range of 5–10 ng/ml. A significant increase in total workload (+52 W min, P=0.009), total exercise time (+32 s, P=0.003) and time to angina (+25 s, P=0.016) was measured with Molsidomine 16 mg o.a.d. relative to placebo. Using linear regression, significant correlation coefficients were determined between Molsidomine plasma concentrations (but not SIN-1) and exercise test improvements (r=0.827, P<0.001 for the total workload; r=0.772, P<0.001 for the total exercise time; and r=0.566, P=0.028 for the time to 1 mm ST-segment depression). The pharmacokinetics of Molsidomine 16 mg in patients with stable angina pectoris is compatible with a o.a.d. dosage regimen. This o.a.d. formulation is effective and well-tolerated, providing a 24-h therapeutic control of myocardial ischemia. A positive and significant linear relationship between Molsidomine plasma concentration and the increase in exercise tolerance was observed.
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acute and chronic effect of Molsidomine extended release on exercise capacity in patients with stable angina a double blind cross over clinical trial versus placebo
Journal of Cardiovascular Pharmacology, 1995Co-Authors: R Messin, Gerard Boxho, J De Smedt, I M BuntinxAbstract:A double-blind, placebo-controlled, cross-over study was performed in 50 patients with ischemic heart disease and stable angina to determine the duration of efficacy of 8 mg Molsidomine in extended-release form. Exercise testing was performed at baseline and 2, 4, 6, 8, and 10 h after intake of either the medication or the placebo. Total duration of exercise (in minutes) and total work performance (workload x min) was significantly improved in the Molsidomine retard group, not only compared with baseline but also with placebo for all time-points. ST segment depression at 60 W and at maximal exercise improved similarly until 10 h after Molsidomine retard treatment. The rate-pressure product (heart rate x systolic blood pressure) showed significant improvement only at 60 W. No attenuation of the obtained effects was observed after 14 days of treatment. The number of anginal attacks and the consumption of sublingual nitroderivates were significantly reduced with Molsidomine retard 8 mg as compared with placebo. Molsidomine retard 8 mg is effective until at least 10 h after oral (p.o.) intake. A dose schedule of Molsidomine retard 8 mg twice daily definitely reduces anginal symptoms.
N A Alyoshina - One of the best experts on this subject based on the ideXlab platform.
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comparative study of adsorption capacity of mesoporous silica materials for Molsidomine effects of functionalizing and solution ph
Materials Science and Engineering: C, 2014Co-Authors: N A Alyoshina, A V Agafonov, Elena V ParfenyukAbstract:Abstract Adsorption capacities of mesoporous silica materials having various surface functional groups (hydroxyl, phenyl, mercaptopropyl, aminopropyl) at pH values of 4.8, 7.4, and 8.0 were studied. It was found that the maximum amount of adsorbed Molsidomine is affected by method of preparation of the silica materials, chemistry of their surfaces and solution pH from where adsorption is carried out. The effects were explained by different states of the adsorbents and Molsidomine in solution at the studied pH. The most efficient adsorption of Molsidomine is observed onto phenyl modified silica prepared by grafting at pH 4.8. Aminopropyl modified silica adsorbs the lowest amount of Molsidomine and the adsorption was observed only at pH 7.4. Interactions responsible for the adsorption were elucidated by spectroscopic studies.
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Functionalized mesoporous silica materials for Molsidomine adsorption: Thermodynamic study
Journal of Solid State Chemistry, 2013Co-Authors: N A Alyoshina, Elena V ParfenyukAbstract:Abstract A series of unmodified and organically modified mesoporous silica materials was prepared. The unmodified mesoporous silica was synthesized via sol–gel synthesis in the presence of d -glucose as pore-forming agent. The functionalized by phenyl, aminopropyl and mercaptopropyl groups silica materials were prepared via grafting. The fabricated adsorbent materials were characterized by Fourier transform infrared spectroscopy (FTIR) analysis, N 2 adsorption/desorption and elemental analysis methods. Then their adsorption properties for mesoionic dug Molsidomine were investigated at 290–313 K and physiological pH value. Thermodynamic parameters of Molsidomine adsorption on the synthesized materials have been calculated. The obtained results showed that the adsorption process of Molsidomine on the phenyl modified silica is the most quantitatively and energetically favorable. The unmodified and mercaptopropyl modified silica materials exhibit significantly higher adsorption capacities and energies for Molsidomine than the aminopropyl modified sample. The effects are discussed from the viewpoint of nature of specific interactions responsible for the adsorption.