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Differences in the production of methemoglobin during high-dose treatment with isosorbide dinitrate or isosorbide
Insights
High doses of isosorbide dinitrate (ISDN) slightly increase methemoglobin (met-Hb) in patients with coronary heart disease, while isosorbide 5-mononitrate (IS-5-MN) does not. This effect was observed acutely and after four days of medication.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Hematology
Background:
- Coronary heart disease (CHD) management often involves nitrates.
- Potential side effects of nitrate therapy, such as methemoglobinemia, require investigation.
- Isosorbide dinitrate (ISDN) and isosorbide 5-mononitrate (IS-5-MN) are commonly used nitrates.
Purpose of the Study:
- To evaluate the impact of high-dose ISDN and IS-5-MN on erythrocyte methemoglobin production in CHD patients.
- To compare the methemoglobin-inducing potential of ISDN versus IS-5-MN in acute and sub-chronic settings.
Main Methods:
- A study involving 12 CHD patients divided into two groups.
- Group 1 received escalating doses of ISDN (80 mg, then 160 mg) acutely and 480 mg/day for 4 days.
- Group 2 received IS-5-MN similarly; methemoglobin levels were measured at various time points.
Main Results:
- IS-5-MN did not significantly alter baseline methemoglobin (met-Hb) levels in acute or sub-chronic administration.
- ISDN administration resulted in a slight, statistically significant increase in met-Hb levels, particularly at higher doses.
- The met-Hb increase with ISDN was observed both in acute experiments and after 4 days of medication.
Conclusions:
- High-dose ISDN may lead to a modest increase in erythrocyte methemoglobin production in CHD patients.
- IS-5-MN appears to have a negligible effect on methemoglobin levels.
- These findings suggest a differential effect of these nitrates on methemoglobin formation, with potential clinical implications for monitoring.
Abstract:
12 patients with coronary heart disease were studied to see whether high doses of isosorbide dinitrate (ISDN, Corovliss) or isosorbide 5-mononitrate (IS-5-MN, Ismo) increase the erythrocyte methemoglobin production in an acute experiment and after 4 days of medication. The patients were divided into two groups. Group 1 (6 patients) was given a single dose of 80 mg ISDN on the morning of day 1 and Group 2 (6 patients) was given 80 mg IS-5-MN as a single oral dose. Under the influence of the IS-5-MN no change was observed from the initial methemoglobin (met-Hb) value (0.81% of the total Hb) at measurements performed 1 and 2 h after the administration of the drug. In Group 1 (ISDN) the initial met-Hb value was 0.58% of the total Hb, a slight increase to 0.70% being observed after 1 h and to 0.77% after 2 h (p less than 0.05). The patients were then treated as follows for a further 4 days: Group 1 480 mg ISDN/d, Group 2 480 mg IS-5-MN/d. On day 5 the initial met-Hb values in both groups were unchanged compared to day 1. The patients were then given first 80 mg ISDN (Group 1) or 80 mg IS-5-MN (Group 2) and 4 h later a single dose of 160 mg of the appropriate substance. In Group 2 (IS-5-MN) the met-Hb content remained unaffected. In Group 1 a slight increase of the met-Hb to 0.79% occurred 1 h after 80 mg ISDN and to 0.9% after 2 h (p less than 0.05). The dose of 160 mg ISDN gave rise to a further slight increase to 1.00% (after 1 h) and 1.13% (after 2 h) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)