Clinical Pharmacokinetics of Once-Daily Molsidomine

Herchuelz, André; Carreer-Bruhwyler, Fabienne; Crommen, Jacques; Chiap, Patrice; Hubert, Philippe; Messin, R; Dubois, Claude; Famaey, Jean-Pierre; Géczy, Joseph

doi:10.2165/00137696-200402020-00005

Cited by 10 publications

(1 citation statement)

References 31 publications

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“…The drug is freely soluble in water (0.25 g/dL À1 at 25 8C) and the duration of antihypertensive action after single oral dosing is only 2.1-2.7 h which necessitates the clinical use of 38-75 mg to be taken at 3-4 times a day [16]. Due to its effectiveness and intensive use as a drug of choice, several controlled release methods of MOL have been reported in the past [17,18]. The combination of inclusion properties of the CyDs and the useful amphiphilic properties of fluorocarbon chains are expected to give molecules possessing novel physical, chemical and biological properties compared to their hydrocarbon analogs.…”

Section: Introductionmentioning

confidence: 99%

Sustained release applications of a fluoroalkyl ester-functionalized amphiphilic cyclodextrin by inclusion complex formation with water-soluble drugs in supercritical carbon dioxide

Ganapathy

Lee

Park

et al. 2008

Journal of Fluorine Chemistry

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Section: Introductionmentioning

confidence: 99%

Sustained release applications of a fluoroalkyl ester-functionalized amphiphilic cyclodextrin by inclusion complex formation with water-soluble drugs in supercritical carbon dioxide

Ganapathy

Lee

Park

et al. 2008

Journal of Fluorine Chemistry

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Tolerability to 1-year treatment with once-daily molsidomine in patients with stable angina

et al. 2006

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Prolonged-release molsidomine 16 mg once daily) QD (has proved effective in the short-term treatment of patients with stable angina. The purpose of this multicenter study was to assess its long-term tolerability and clinical effectiveness. A total of 320 patients with stable angina were treated for 1 year with molsidomine 16 mg QD administered open label as monotherapy or add-on therapy, when beta blockers and/or calcium antagonists were prescribed concomitantly) in 128 patients, ie, 40% of cases), depending on the severity of disease and/or local therapeutic policies. In all, 293 patients (91.6%) completed the study. The proportion of patients who reported drug-related adverse events (AEs) was 9.1%, which is not significantly different (P=.13) from the 5.9% observed during previous short-term (2-4 wk) treatment. Headache accounted for 80.6% of all drug-related AEs and required discontinuation of the drug in one quarter of patients who reported the symptom (ie, 1.9% of the 320 patients involved in the study). No serious drug-related AEs occurred during the study. Tolerability to molsidomine, evaluated with use of a visual analog scale (VAS), improved by 20% from beginning to end of 1-year follow-up. Two-by-two Bonferroni's comparisons were significant at the .05 level between the 2-month assessment and assessments performed at 8, 10, and 12 months. No age-time interaction was noted (P=.82). Heart rate, blood pressure, electrocardiogram, and blood parameters showed no statistically significant or clinically relevant changes during the study. Compliance with treatment was satisfactory throughout the follow-up period. There was no significant change in the weekly frequency of anginal attacks and consumption of short-acting nitroderivatives during the 1-year study (P=.07 and P=.12,respectively), but their frequency was significantly (ie, approximately 50%) lower than during a preceding short-term treatment period (P<.0001 and P=.014, respectively). Subjective clinical status, evaluated through an appropriate VAS, improved by 38% from start to end of 1-year follow-up. Bonferroni's comparisons between baseline and subsequent 2-month evaluations were all significant at the .05 level. No age-time interaction could be seen for frequency of anginal attacks and consumption of short-acting nitroderivatives, nor for clinical status )P=.10, P=.11, and P=.51, respectively). Neither tolerability to molsidomine nor effectiveness of the drug was biased by concomitant antianginal therapies, insofar as none of these parameters showed a significant treatment type (ie, molsidomine administered as monotherapy or add-on therapy)-time interaction (VAS for tolerability: P=.44; angina: P=.39; nitroderivatives: P=.72; VAS for clinical status: P=.62). Molsidomine 16 mg QD administered for 1 y to patients with stable angina was well tolerated and remained effective during the entire treatment period, independent of age and concomitant antianginal therapy.

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Efficacy and safety of once- and twice-daily formulations of molsidomine in patients with stable angina pectoris: Double-blind and open-label studies

et al. 2006

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Molsidomine, a sydnonimine acting as a heterocyclic direct nitric oxide donor, has been used for many years in several European countries for the treatment of patients with stable angina pectoris. The efficacy and tolerability of a novel once-daily 16-mg formulation of molsidomine (M16) were compared with those of the currently used twice-daily 8-mg molsidomine tablet (M8) in 666 patients. Study 1, a multicenter, randomized, double-blind, placebo-controlled, twin crossover study, involved 533 patients given acute and 2-week treatment with each drug formulation. Study 2, a multicenter, open-label, sequential, add-on trial, compared M16 and M8 in 133 patients. Drug effects on exercise capacity (study 1 only), frequency of anginal attacks and consumption of short-acting itroderivatives, and incidence of adverse events (AEs) were evaluated. Compared with placebo, M16 increased exercise capacity by 15% (P<.001) at the start of study 1 and by 13% (P<.001) after 2 weeks' treatment, and was not inferior to M8. In terms of anginal attack frequency and nitroderivative consumption, M16 was not inferior to M8 in either study. Moreover, compared with M8, M16 produced a statistically and clinically significant reduction in the incidence of anginal attacks in elderly (>/=75 y) but not in younger patients (<75 y) (study 2), nor in patients from study 1. No significant difference from M8 was found in either study in short-acting nitroderivative consumption. No tolerance to M8 or M16 was observed after 2-week treatment. No statistically significant differences in incidences of all AEs and drug-related AEs were observed between M16 and M8 in either study. The same held true for proportions of patients experiencing AEs and drug-related AEs on M16 vs M8: in study 1-14.3% and 11.8% for all AEs (P=.218), 6.9% and 5.4% for drug-related AEs (P=.280); in study 2-1.3% and 1.3% for all AEs, 0% and 1.3% for drug-related AEs (P>.10) in young patients; and in the elderly, 3.6% and 0% for drug-related AEs (P>.10). Only the proportion of elderly patients with all AEs was significantly higher with M16 than with M8: 14.5% vs 1.8% (P=.039). M16 once daily was effective and well tolerated in investigated patients with stable angina pectoris, particularly the elderly, affording 24 hours of therapeutic activity. M16 was not inferior to M8 given twice daily in terms of efficacy, safety profile, and tolerability.

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Clinical Pharmacokinetics of Once-Daily Molsidomine

Cited by 10 publications

References 31 publications

Sustained release applications of a fluoroalkyl ester-functionalized amphiphilic cyclodextrin by inclusion complex formation with water-soluble drugs in supercritical carbon dioxide

Sustained release applications of a fluoroalkyl ester-functionalized amphiphilic cyclodextrin by inclusion complex formation with water-soluble drugs in supercritical carbon dioxide

Tolerability to 1-year treatment with once-daily molsidomine in patients with stable angina

Efficacy and safety of once- and twice-daily formulations of molsidomine in patients with stable angina pectoris: Double-blind and open-label studies

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