Isosorbide dinitrate

Identification

Summary

Isosorbide dinitrate is a vasodilator used to treat angina in coronary artery disease.

Brand Names
Bidil, Dilatrate, Isordil
Generic Name
Isosorbide dinitrate
DrugBank Accession Number
DB00883
Background

A vasodilator used in the treatment of angina pectoris. Its actions are similar to nitroglycerin but with a slower onset of action.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 236.1363
Monoisotopic: 236.028065242
Chemical Formula
C6H8N2O8
Synonyms
  • 1,4:3,6-Dianhydrosorbitol 2,5-dinitrate
  • D-Isosorbide dinitrate
  • Dianhydrosorbitol 2,5-dinitrate
  • Dinitrate d'isosorbide
  • Dinitrato de isosorbida
  • Dinitroisosorbide
  • Dinitrosorbide
  • ISDN
  • Isosorbide 2,5-dinitrate
  • Isosorbide dinitrate
  • Isosorbidi dinitras
  • Sorbide nitrate
  • Sorbidnitrate
External IDs
  • C01DA08

Pharmacology

Indication

For the prevention of angina pectoris due to coronary artery disease.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure.

Mechanism of action

Isosorbide dinitrate is converted to the active nitric oxide to activate guanylate cyclase. This activation increases levels of cyclic guanosine 3',5'-monophosphate (cGMP). cGMP activates protein kinases and causes a series of phosphorylation reactions which leads to dephosphorylation of myosin light chains of smooth muscle fibres. Finally there is a release of calcium ions which causes smooth muscle relaxation and vasodilation.

TargetActionsOrganism
AAtrial natriuretic peptide receptor 1
agonist
Humans
Absorption

Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver. The average bioavailability of isosorbide dinitrate is about 25%.

Volume of distribution
  • 2 to 4 L/kg
Protein binding

Very low

Metabolism

Hepatic

Route of elimination

Not Available

Half-life

1 hour

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include reduced cardiac output and hypotension.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololThe risk or severity of adverse effects can be increased when Isosorbide dinitrate is combined with Acebutolol.
AcetaminophenIsosorbide dinitrate may increase the hepatotoxic activities of Acetaminophen.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Isosorbide dinitrate.
AliskirenThe risk or severity of adverse effects can be increased when Isosorbide dinitrate is combined with Aliskiren.
AmbrisentanIsosorbide dinitrate may increase the hypotensive activities of Ambrisentan.
AmifostineThe risk or severity of adverse effects can be increased when Isosorbide dinitrate is combined with Amifostine.
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Isosorbide dinitrate.
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Isosorbide dinitrate.
AmiodaroneIsosorbide dinitrate may increase the vasodilatory activities of Amiodarone.
AmlodipineIsosorbide dinitrate may increase the vasodilatory activities of Amlodipine.
Interactions
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Food Interactions
  • Take with or without food. Food decreases drug absorption.

Products

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Active Moieties
NameKindUNIICASInChI Key
IsosorbideunknownWXR179L51S652-67-5KLDXJTOLSGUMSJ-JGWLITMVSA-N
Product Images
International/Other Brands
Carvasin (Ayerst) / Flindix (Vitória) / Isoket (Schwarz) / Isorbid (Armstrong) / Nitrosorbide (Lusofarmaco) / Sorbidilat (Actavis)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Cedocard-SR Srt 20mgTablet, extended release20 mgOralPaladin Labs Inc1987-12-312009-08-07Canada flag
Cedocard-SR Srt 40mgTablet, extended release40 mgOralPaladin Labs Inc1995-12-312009-08-07Canada flag
Coradur Tab 20mgTablet, extended release20 mgOralGlaxo Canada Inc1987-12-311997-04-25Canada flag
CoronexTablet30 mgOralWyeth Ltd.1994-12-312007-01-08Canada flag
CoronexTablet10 mgOralWyeth Ltd.1994-12-312007-01-08Canada flag
Coronex 5mg Sublingual TabletsTablet5 mgSublingualWyeth Ltd.1994-12-312007-01-08Canada flag
Dilatrate SRCapsule40 mg/1OralAuxilium Pharmaceuticals, Inc.2014-10-242015-10-15US flag
Dilatrate SRCapsule, extended release40 mg/1OralEndo Pharmaceuticals Inc.2012-02-152021-08-31US flag
Dilatrate-SRCapsule, extended release40 mg/1OralSchwarz Pharma2008-01-23Not applicableUS flag0091 092020180818 17235 br9l0e
IsdnTablet10 mgOralAa Pharma Inc1982-12-31Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IsoDitrateTablet, extended release40 mg/1OralAmedra Pharmaceuticals2010-04-302010-04-30US flag
IsosorbideTablet20 mg/1OralGolden State Medical Supply, Inc.1987-11-022017-01-02US flag
IsosorbideTablet20 mg/1OralCardinal Health1987-10-292012-10-31US flag
IsosorbideTablet5 mg/1OralHikma Pharmaceutical1978-12-01Not applicableUS flag
IsosorbideTablet5 mg/1OralMed Health Pharma LLC.2011-03-022012-04-15US flag
IsosorbideTablet20 mg/1OralBluePoint Laboratories2018-11-30Not applicableUS flag
IsosorbideTablet10 mg/1OralCardinal Health1987-10-292012-10-31US flag
IsosorbideTablet10 mg/1OralGolden State Medical Supply, Inc.1987-10-262017-01-02US flag00143 1771 10 nlmimage10 71083881
IsosorbideTablet20 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
IsosorbideTablet20 mg/1OralHikma Pharmaceutical1983-04-26Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BiDilIsosorbide dinitrate (20 mg/1) + Hydralazine hydrochloride (37.5 mg/1)Tablet, film coatedOralRemedy Repack2013-10-082013-10-09US flag
BiDilIsosorbide dinitrate (20 mg/1) + Hydralazine hydrochloride (37.5 mg/1)Tablet, film coatedOralArbor Pharmaceuticals, Inc.2012-12-05Not applicableUS flag24338 01020180907 15195 ecm0g8
BiDilIsosorbide dinitrate (20 mg/1) + Hydralazine hydrochloride (37.5 mg/1)Tablet, film coatedOralArbor Pharmaceuticals2005-06-232015-12-31US flag12948 0001 12 nlmimage10 2f131798

Categories

ATC Codes
C01DA08 — Isosorbide dinitrateC01DA58 — Isosorbide dinitrate, combinationsC05AE02 — Isosorbide dinitrate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as isosorbides. These are organic polycyclic compounds containing an isosorbide(1,4-Dianhydrosorbitol) moiety, which consists of two -oxolan-3-ol rings.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Furofurans
Sub Class
Isosorbides
Direct Parent
Isosorbides
Alternative Parents
Tetrahydrofurans / Alkyl nitrates / Organic nitro compounds / Organic nitric acids and derivatives / Oxacyclic compounds / Dialkyl ethers / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives
Substituents
Aliphatic heteropolycyclic compound / Alkyl nitrate / Allyl-type 1,3-dipolar organic compound / Dialkyl ether / Ether / Hydrocarbon derivative / Isosorbide / Organic 1,3-dipolar compound / Organic nitrate / Organic nitric acid or derivatives
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
nitrate ester, glucitol derivative (CHEBI:6061)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
IA7306519N
CAS number
87-33-2
InChI Key
MOYKHGMNXAOIAT-JGWLITMVSA-N
InChI
InChI=1S/C6H8N2O8/c9-7(10)15-3-1-13-6-4(16-8(11)12)2-14-5(3)6/h3-6H,1-2H2/t3-,4+,5-,6-/m1/s1
IUPAC Name
(3R,3aS,6S,6aS)-6-(nitrooxy)-hexahydrofuro[3,2-b]furan-3-yl nitrate
SMILES
[H][C@]12OC[C@H](O[N+]([O-])=O)[C@@]1([H])OC[C@H]2O[N+]([O-])=O

References

Synthesis Reference

Gunter Cordes, Ulrich Munch, Ewald Giesselmann, "Supersaturated isosorbide dinitrate solution, process for its production and its use." U.S. Patent US4156736, issued August, 1976.

US4156736
General References
Not Available
Human Metabolome Database
HMDB0015021
KEGG Drug
D00516
KEGG Compound
C07456
PubChem Compound
6883
PubChem Substance
46506412
ChemSpider
6619
RxNav
6058
ChEBI
6061
ChEMBL
CHEMBL6622
ZINC
ZINC000018089317
Therapeutic Targets Database
DAP001057
PharmGKB
PA450125
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Isosorbide_dinitrate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic SciencePost-anesthesia Recovery1
4CompletedPreventionAdverse Side Effects / Coronary Artery Atherosclerosis / Insulin resistance syndrome1
4CompletedPreventionChronic Hemodialysis (ESRD)1
4CompletedTreatmentCongestive Heart Failure (CHF)1
4CompletedTreatmentCoronary Artery Stenosis / Coronary Heart Disease (CHD)1
4CompletedTreatmentMaternal Care for Late Fetal Death / Pregnancy, Cornual1
4RecruitingTreatmentDiabetes / Heart Failure1
3CompletedTreatmentCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Myocardial Ischemia1
3CompletedTreatmentDiabetic Foot Ulcers (DFU)1
3CompletedTreatmentHeart Failure / High Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
  • Schwarz pharma inc
  • Wyeth ayerst laboratories
  • Astrazeneca pharmaceuticals lp
  • Caraco pharmaceutical laboratories ltd
  • Corepharma llc
  • Biovail laboratories inc
  • Mutual pharmaceutical co inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Superpharm corp
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • West ward inc
Packagers
  • Amedra Pharmaceuticals LLC
  • Amerisource Health Services Corp.
  • Atlantic Biologicals Corporation
  • Bryant Ranch Prepack
  • BTA Pharmaceuticals
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Consolidated Midland Corp.
  • Corepharma LLC
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Forest Pharmaceuticals
  • Golden State Medical Supply Inc.
  • H and H Laboratories
  • Heartland Repack Services LLC
  • Hikma Pharmaceuticals
  • Inwood Labs
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Meda AB
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neighborcare Repackaging Inc.
  • Nitromed Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Rising Pharmaceuticals
  • Sandhills Packaging Inc.
  • Sandoz
  • Schwarz Pharma Inc.
  • Southwood Pharmaceuticals
  • Talbert Medical Management Corp.
  • Tya Pharmaceuticals
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
SolutionIntravenous; Parenteral
Tablet, delayed release
TabletOral; Sublingual
Tablet
Tablet, extended releaseOral
CapsuleOral40 mg/1
Capsule, extended releaseOral40 mg/1
Injection, solution, concentrateIntravenous; Parenteral
TabletOral40 mg
TabletOral30 mg
Capsule, extended releaseOral40 mg
Capsule, extended releaseOral20 MG
Capsule, extended releaseOral60 MG
Tablet5 MG
Tablet20 MG
Tablet40 MG
TabletOral10 mg
Tablet, orally disintegratingSublingual5 MG
InjectionIntracoronary; Intravenous
Capsule, extended releaseOral120 MG
Tablet, extended releaseOral20 MG
Tablet, extended releaseOral40 MG
Capsule, extended releaseOral80 MG
Capsule, coated pelletsOral
TabletSublingual
InjectionIntravenous
Tablet, extended releaseOral40 mg/1
TabletOral2.5 mg/1
TabletOral40 mg/1
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
TabletOral
TabletOral30 mg/1
TabletSublingual2.5 mg/1
TabletSublingual5 mg/1
TabletTransmucosal
CapsuleOral
Cream40 G
Injection, solutionIntravenous; Parenteral
Tablet30 mg
TabletSublingual5 mg
Tablet10 mg
Prices
Unit descriptionCostUnit
Isordil Titradose 40 mg tablet1.7USD tablet
Isordil 40 mg tablet1.58USD tablet
Dilatrate-sr 40 mg capsule1.48USD capsule
Isochron 40 mg tablet sa1.07USD tablet
Isosorbide Dinitrate CR 40 mg Controlled Release Tabs0.88USD tab
Isosorbide Mononitrate 20 mg tablet0.78USD tablet
Isosorbide Mononitrate 10 mg tablet0.74USD tablet
Isordil Titradose 5 mg tablet0.68USD tablet
Isordil 5 mg tablet0.65USD tablet
Isosorbide dn 30 mg tablet0.53USD tablet
Isordil 10 mg tablet0.5USD tablet
Isosorbide Dinitrate 30 mg tablet0.5USD tablet
Cedocard-Sr 20 mg Sustained-Release Tablet0.44USD tablet
Isosorbide Dinitrate 10 mg tablet0.43USD tablet
Isosorbide Dinitrate 20 mg tablet0.43USD tablet
Isosorbide Dinitrate 2.5 mg Sublingual Tabs0.39USD tab
Isosorbide Dinitrate 5 mg Sublingual Tabs0.21USD tab
Isosorbide dn 2.5 mg tablet sl0.21USD tablet
Isosorbide dn 5 mg tablet sl0.21USD tablet
Isosorbide dn 20 mg tablet0.2USD tablet
Isosorbide Dinitrate 5 mg tablet0.17USD tablet
Isosorbide dn 10 mg tablet0.17USD tablet
Isosorbide dn 5 mg tablet0.17USD tablet
Apo-Isdn 30 mg Tablet0.09USD tablet
Apo-Isdn 5 mg Sublingual Tablet0.07USD tablet
Apo-Isdn 10 mg Tablet0.04USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6465463No2002-10-152020-09-08US flag
US6784177No2004-08-312020-09-08US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)70 °CPhysProp
water solubility550 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.31HANSCH,C ET AL. (1995)
logS-2.63ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.938 mg/mLALOGPS
logP0.87ALOGPS
logP-0.0096ChemAxon
logS-2.4ALOGPS
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area123.2 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity42.76 m3·mol-1ChemAxon
Polarizability18.15 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.935
Blood Brain Barrier+0.9559
Caco-2 permeable-0.5746
P-glycoprotein substrateNon-substrate0.8064
P-glycoprotein inhibitor INon-inhibitor0.6173
P-glycoprotein inhibitor IINon-inhibitor0.8911
Renal organic cation transporterNon-inhibitor0.8453
CYP450 2C9 substrateNon-substrate0.9057
CYP450 2D6 substrateNon-substrate0.9021
CYP450 3A4 substrateSubstrate0.5298
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9534
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9538
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7116
BiodegradationReady biodegradable0.7633
Rat acute toxicity2.4849 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5057
hERG inhibition (predictor II)Non-inhibitor0.9381
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Protein kinase activity
Specific Function
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate ...
Gene Name
NPR1
Uniprot ID
P16066
Uniprot Name
Atrial natriuretic peptide receptor 1
Molecular Weight
118918.11 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Villarroya M, Lopez MG, de Pascual R, Garcia AG: Preclinical profile of PF9404C, a nitric oxide donor with beta receptor blocking properties. Cardiovasc Drug Rev. 2005 Summer;23(2):149-60. [Article]
  4. Takabuchi S, Hirota K, Nishi K, Oda S, Oda T, Shingu K, Takabayashi A, Adachi T, Semenza GL, Fukuda K: The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway. Biochem Biophys Res Commun. 2004 Nov 5;324(1):417-23. [Article]
  5. Beauregard C, Brandt PC, Chiou GC: Nitric oxide and cyclic GMP-mediated protein secretion from cultured lacrimal gland acinar cells. J Ocul Pharmacol Ther. 2002 Oct;18(5):429-43. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Vuppugalla R, Mehvar R: Selective effects of nitric oxide on the disposition of chlorzoxazone and dextromethorphan in isolated perfused rat livers. Drug Metab Dispos. 2006 Jul;34(7):1160-6. doi: 10.1124/dmd.105.009050. Epub 2006 Apr 18. [Article]

Drug created on June 13, 2005 13:24 / Updated on July 24, 2021 14:57