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Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: a review. DUMQOL (DUtch Mononitrate
T J Cleophas1, M G Niemeyer, A H Zwinderman
1European Interuniversity College of Pharmaceutical Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
Abstract:
Since the first publication of isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation in 1985, a considerable body of literature concerning its clinical efficacy and safety has become available. Theoretically, the formulation has the advantage over conventional isosorbide mononitrate or dinitrate (ISMN/ISDN) that it has a simpler and more predictable pharmacokinetic profile. The objectives of this paper are to review published data so far and to see whether the theoretical advantages translate into better clinical effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a rapid onset of action (30 minutes), and effects are evident for up to 17 hours. 2. The antianginal effects of once-daily isosorbide mononitrate IR-SR increased with increasing dosages, were generally larger than those of either placebo or equipotent doses of conventional ISMN/ISDN, and were somewhat larger than those of the beta blocker bupranolol. The effects were generally similar to those of sustained release nifedipine. 3. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate IR-SR than with twice or three times daily regimens of conventional ISMN/ISDN. This was particularly so with mobility, psychological distress, and life satisfaction indices. 4. Tolerance did not develop after 13 months of once daily isosorbide dinitrate IR-SR. No rebound increase in incidence of ischemic episodes was observed after discontinuation of treatment. 5. Long-term efficacy data both of isosorbide mononitrate IR-SR and of conventional ISMN/ISDN are limited so far. Large studies in patients with angina pectoris and patients with heart failure addressing long-term effects are ongoing, and some of the data will be completed within the next months. Isosorbide mononitrate IR-SR has a rapid onset of action and has been shown to be clinically efficient and, in addition, to be more so than conventional ISMN / ISDN. Nitrate tolerance with continued use of the formulation has not yet been reported. Long-term effects on morbidity and mortality are currently being assessed.
Insights
Isosorbide mononitrate IR-SR offers rapid action and superior antianginal effects compared to conventional ISMN/ISDN. This formulation improves quality of life and shows no signs of tolerance, with long-term data pending.
Area of Science:
- Pharmacology
- Cardiology
- Clinical Pharmacy
Background:
- Isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation introduced in 1985.
- Theoretical advantages over conventional isosorbide mononitrate or dinitrate (ISMN/ISDN) include simpler pharmacokinetics.
Purpose of the Study:
- Review published data on isosorbide mononitrate IR-SR efficacy and safety.
- Evaluate if theoretical pharmacokinetic advantages translate to improved clinical effectiveness.
Main Methods:
- Review of published literature on isosorbide mononitrate IR-SR.
- Comparison of antianginal effects, quality-of-life indices, and tolerance with placebo, conventional ISMN/ISDN, bupranolol, and sustained-release nifedipine.
Main Results:
- Isosorbide mononitrate IR-SR demonstrated rapid onset (30 min) and prolonged action (up to 17 hours).
- Antianginal effects were dose-dependent, superior to placebo and conventional ISMN/ISDN, and comparable to sustained-release nifedipine.
- Significant improvements in quality-of-life indices (mobility, psychological distress, life satisfaction) were observed with once-daily IR-SR.
- No tolerance developed after 13 months of once-daily use, and no rebound ischemia occurred upon discontinuation.
Conclusions:
- Isosorbide mononitrate IR-SR is clinically effective, offering faster onset and greater efficacy than conventional ISMN/ISDN.
- The formulation enhances patient quality of life without reported nitrate tolerance.
- Ongoing large studies will assess long-term effects on morbidity and mortality.