Absorption, Distribution and Excretion
Upon oral administration, isosorbide mononitrate is rapidly and completely absorbed from the gastrointestinal tract. Isosorbide mononitrate has a dose-linear kinetics and the absolute bioavailability is nearly 100%. The Cmax is reached within 30 to 60 minutes following administration.
In a human radio-labelled drug study, about 93% of the total dose was excreted in the urine within 48 hours. Following oral administration of 20 mg, only 2% of isosorbide mononitrate was excreted unchanged in the urine within 24 hours. Among the excreted dose, nearly half of the dose was found de-nitrated in urine as isosorbide and sorbitol: approximately 30% is excreted as isosorbide and about 17% is the 2-glucuronide of mononitrate. These metabolites were not vasoactive or pharmacologically active. Renal excretion was complete after 5 days, and fecal excretion accounted for only 1% of drug elimination.
The volume of distribution is approximately 0.6 L/kg, which is approximately the volume of total body water.
The total body clearance is 115-120 mL/min.

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Metabolism / Metabolites
Isosorbide mononitrate is not subject to first pass metabolism in human liver. Detectable metabolites include isosorbide, sorbitol, and 2-glucuronide of mononitrate, which are pharmacologically inactive.

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Biological Half-Life
The elimination half-life of isosorbide mononitrate is about 5 hours. The elimination half-life of its metabolites, isosorbide and 2-glucuronide of mononitrate, are 8 hours and 6 hours, respectively.

Protein Binding
Isosorbide mononitrate is about 5% bound to plasma proteins.

Isosorbide-5-mononitrate is a crystalline solid. It is very flammable and may be toxic by ingestion.
Isosorbide mononitrate is a nitrate ester and a glucitol derivative. It has a role as a nitric oxide donor and a vasodilator agent.
Isosorbide mononitrate is an organic nitrate with vasodilating properties. It is an anti-anginal agent that works by relaxing the smooth muscles of both arteries and veins, but but predominantly veins to reduce cardiac preload. Isosorbide mononitrate is an active metabolite of [isosorbide dinitrate]. Like other organic nitrates, isosorbide mononitrate acts as a prodrug for its active metabolite, [nitric oxide], which mediates the therapeutic action of isosorbide mononitrate. Isosorbide mononitrate has a longer duration of action than [nitroglycerin] due to its slow onset of absorption and metabolism. First approved by the FDA in 1991, isosorbide mononitrate is used for the prevention and management of angina pectoris caused by coronary artery disease; however, the onset of action of orally-administered isosorbide mononitrate is not rapid enough to offset an acute anginal episode. It is available in oral tablets generically and under the brand name ISMO and Monoket. The extended-release forms of the drug are also available generically and under the brand name Imdur.
Isosorbide mononitrate is a Nitrate Vasodilator. The physiologic effect of isosorbide mononitrate is by means of Vasodilation.
Isosorbide Mononitrate is the mononitrate salt form of isosorbide, an organic nitrate with vasodilator activity. Isosorbide mononitrate relaxes vascular smooth muscle by formation of the free radical nitric oxide (NO), which is identical to the endothelium-derived relaxing factor (EDRF). NO activates guanylyl cyclase, thereby increasing the synthesis of cGMP within smooth muscle, resulting in dephosphorylation of light chain myosin and relaxation of peripheral arteries and veins. In addition, isosorbide mononitrate relaxes coronary arteries, thereby increasing the blood circulation through the ischemic area. (NCI05)
See also: Isosorbide (has active moiety).

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Drug Indication
Isosorbide mononitrate is indicated for the prevention and management of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid to be useful in aborting an acute anginal episode.
FDA Label

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Mechanism of Action
Isosorbide mononitrate acts as a prodrug for nitric oxide (NO), which is a potent vasodilator gas that is released when the drug is metabolized. NO activates soluble guanylyl cyclase in vascular endothelial cells, which increases the intracellular concentrations of cyclic GMP (cGMP). cGMP activates cGMP-dependent protein kinases, such as protein kinase G and I, which activates the downstream intracellular cascades. The downstream cascade results in reduced intracellular concentrations of calcium, caused by processes including inhibition of IP₃-mediated pathway, phosphorylation of big calcium-activated potassium channel leading to cell hyperpolarization and reduced calcium influx, and increased calcium efflux via the Ca2+-ATPase-pump. Reduced intracellular calcium concentrations lead to the dephosphorylation of myosin light chains and the relaxation of smooth muscle cells.

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Pharmacodynamics
Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. The pharmacological action is mediated by the active metabolite, [nitric oxide], which is released when isosorbide mononitrate is metabolized. Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload. In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness. At therapeutic doses of isosorbide mononitrate, nitric oxide has a bigger effect on larger muscular arteries over small resistance arteries. Arterial relaxation leads to reduced systemic vascular resistance and systolic blood (aortic) pressure, decreasing to decreased cardiac afterload. The direct dilator effect on coronary arteries opposes the coronary artery spasm in variant angina or angina pectoris. At larger doses, nitric oxide causes the resistance arteries and arterioles to dilate, reducing arterial pressure via coronary vasodilatation. This leads to increased coronary blood flow. Reduced cardiac preload and afterload caused by nitric oxide causes a reduction in myocardial oxygen consumption; decreased myocardial oxygen demand, along with increased coronary blood flow, leads to an increased in the oxygen content of coronary sinus blood and the relief from ischemia. The end effect of isosorbide mononitrate include decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms. Nitric oxide can also increase the rate of relaxation of cardiac muscles, which is an effect outside of vascular smooth muscles. Organic nitrates can also relax other types of smooth muscles, including esophageal and biliary smooth muscle. The anti-anginal activity of isosorbide mononitrate was observed about 1 hour after dosing, and the peak effect was achieved from 1-4 hours after dosing. The duration of anti-anginal action of at least 12 hours was observed with an asymmetrical dosing regimen.

C6H9NO6

191.139

191.042

16051-77-7

Isosorbide;652-67-5

27661

White to off-white solid powder

1.6±0.1 g/cm3

364.5±42.0 °C at 760 mmHg

88-93 °C

174.2±27.9 °C

0.0±1.8 mmHg at 25°C

1.543

-0.51

1

6

1

13

216

4

O1C([H])([H])[C@]([H])([C@]2([H])[C@@]1([H])[C@]([H])(C([H])([H])O2)O[H])O[N+](=O)[O-]

YWXYYJSYQOXTPL-SLPGGIOYSA-N

InChI=1S/C6H9NO6/c8-3-1-11-6-4(13-7(9)10)2-12-5(3)6/h3-6,8H,1-2H2/t3-,4+,5+,6+/m0/s1

[(3S,3aR,6R,6aS)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate

BM 22-145; AHR-4698; AHR 4698

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~523.18 mM)
H2O : ~50 mg/mL (~261.59 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (13.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (13.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 33.33 mg/mL (174.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)