Identification

Name
Diltiazem
Accession Number
DB00343  (APRD00473)
Type
Small Molecule
Groups
Approved, Investigational
Description

A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic.

Structure
Thumb
Synonyms
  • (+)-cis-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate ester
  • (2S-cis)-3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
  • (2S,3S)-5-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate
  • Acetic acid (2S,3S)-5-(2-dimethylamino-ethyl)-2-(4-methoxy-phenyl)-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]thiazepin-3-yl ester
  • D-cis-diltiazem
  • Diltiazem
  • Diltiazemum
Product Ingredients
IngredientUNIICASInChI Key
Diltiazem hydrochlorideOLH94387TE33286-22-5HDRXZJPWHTXQRI-BHDTVMLSSA-N
Diltiazem malate14Y6444DRP144604-00-2IUSFTUWHKCSCDY-QTKZZPNDSA-N
Diltiazem maleate896626Q8XW139492-78-7WHBXLOWLFLTDMD-WECFPGDBSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Diltiazem CDCapsule, extended release180 mgOralTeva2011-10-06Not applicableCanada
Act Diltiazem CDCapsule, extended release300 mgOralTeva2011-10-06Not applicableCanada
Act Diltiazem CDCapsule, extended release120 mgOralTeva2011-10-06Not applicableCanada
Act Diltiazem CDCapsule, extended release240 mgOralTeva2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended release240 mgOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended release120 mgOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended release360 mgOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended release300 mgOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended release180 mgOralActavis Pharma Company2011-10-06Not applicableCanada
Apo Diltiaz Tab 30mgTablet30 mgOralApotex Corporation1988-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alti-diltiazem Tab 30mgTablet30 mgOralAltimed Pharma Inc.1990-12-312005-05-27Canada
Alti-diltiazem Tab 60mgTablet60 mgOralAltimed Pharma Inc.1990-12-312005-05-27Canada
Apo-diltiaz CDCapsule, extended release120 mgOralApotex Corporation1997-03-27Not applicableCanada
Apo-diltiaz CDCapsule, extended release240 mgOralApotex Corporation1997-03-27Not applicableCanada
Apo-diltiaz CDCapsule, extended release180 mgOralApotex Corporation1997-03-27Not applicableCanada
Apo-diltiaz CD - Cap 300mgCapsule, extended release300 mgOralApotex Corporation1996-09-12Not applicableCanada
Apo-diltiaz InjectableLiquid5 mgIntravenousApotex Corporation2000-06-202013-08-02Canada
Apo-diltiaz SR - 90mg/srcCapsule, extended release90 mgOralApotex Corporation1996-09-19Not applicableCanada
Apo-diltiaz SR - Src 120mgCapsule, extended release120 mgOralApotex Corporation1996-09-19Not applicableCanada
Apo-diltiaz SR - Src 60mgCapsule, extended release60 mgOralApotex Corporation1996-09-19Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Diltiazem HClDiltiazem hydrochloride (1 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2011-09-302017-12-06Us
Diltiazem HClDiltiazem hydrochloride (0.83 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2013-10-22Not applicableUs
Diltiazem HydrochlorideDiltiazem hydrochloride (180 mg/1)Capsule, extended releaseOralRemedy Repack2011-08-172012-01-18Us
International/Other Brands
Acalix (Roemmers) / Adizem (Mundipharma) / Altiazem (Lusofarmaco) / Anoheal / Calcicard / Cartia / Dilacor / Dilacor-XR (Watson) / Dilcontin (Modi-Mundipharma) / Dilrene (Sanofi) / Diltia XT / Dilticard (Intra) / Dilzem (Pfizer) / Herbesser (Mitsubishi Tanabe) / Incoril AP (Bago) / Masdil (Esteve) / Surazem / TAZTIA / Tildem / Viazem (Biovail)
Categories
UNII
EE92BBP03H
CAS number
42399-41-7
Weight
Average: 414.518
Monoisotopic: 414.16132802
Chemical Formula
C22H26N2O4S
InChI Key
HSUGRBWQSSZJOP-RTWAWAEBSA-N
InChI
InChI=1S/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1
IUPAC Name
(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate
SMILES
COC1=CC=C(C=C1)[C@@H]1SC2=C(C=CC=C2)N(CCN(C)C)C(=O)[C@@H]1OC(C)=O

Pharmacology

Indication

For the treatment of Hypertension

Associated Conditions
Pharmacodynamics

Diltiazem, a benzothiazepine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Diltiazem is a non-dihydropyridine (DHP)member of the calcium channel blocker class, along with Verapamil. Diltiazem is similar to other peripheral vasodilators. Diltiazem inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Mechanism of action

Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.

TargetActionsOrganism
AVoltage-dependent calcium channel gamma-1 subunit
inhibitor
Human
Absorption

Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.

Volume of distribution
Not Available
Protein binding

70%-80%

Metabolism

Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.

Route of elimination
Not Available
Half life

3.0 - 4.5 hours

Clearance
Not Available
Toxicity

LD50=740mg/kg (orally in mice)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Diltiazem Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Beta-1 adrenergic receptor---(C;G) / (G;G)C > GEffect Directly StudiedPatients with this genotype require a lower dosage of diltiazem to achieve a favourable rate-control response when treating atrial fibrillation.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Diltiazem.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Diltiazem.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Diltiazem is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Diltiazem.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Diltiazem.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Diltiazem.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Diltiazem.
6-Deoxyerythronolide BThe metabolism of Diltiazem can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Diltiazem.
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Diltiazem.
Food Interactions
  • Avoid natural licorice.
  • Take this medication 30 minutes before meals.

References

Synthesis Reference

Kugita, H., Inoue, H., Ikezaki, M. and Takeo, S.; U.S. Patent 3,562,257; assigned to Tanabe Seiyaku Co.,Ltd., Japan.

US3562257
General References
Not Available
External Links
Human Metabolome Database
HMDB0014487
KEGG Drug
D07845
KEGG Compound
C06958
PubChem Compound
39186
PubChem Substance
46505667
ChemSpider
35850
BindingDB
50004704
ChEBI
101278
ChEMBL
CHEMBL23
Therapeutic Targets Database
DAP001262
PharmGKB
PA449334
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Diltiazem
ATC Codes
C05AE03 — DiltiazemC08DB01 — Diltiazem
AHFS Codes
  • 24:28.92 — Miscellaneous Calcium-channel Blocking Agents
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingPreventionInduction of intra-operative hypotension1
1CompletedNot AvailableNonvalvular Atrial Fibrillation1
1CompletedNot AvailableSubstance, Addiction1
1CompletedBasic ScienceDrug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedBasic ScienceHealthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein1
1CompletedBasic ScienceThrombotic events1
1CompletedOtherDrug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentAtherosclerosis1
1CompletedTreatmentCLARITHROMYCIN/DILTIAZEM [VA Drug Interaction]1
1CompletedTreatmentCardiovascular Disease (CVD) / High Blood Pressure (Hypertension) / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1CompletedTreatmentPharmacokinetics1
1TerminatedOtherHealthy Volunteers1
1TerminatedTreatmentFood Intake1
1Unknown StatusTreatmentAdult Subjects With Anal Fissures1
1Unknown StatusTreatmentDiltiazem Skin Sensitivity1
1Unknown StatusTreatmentSkin Irritation1
1WithdrawnTreatmentHepatitis C Viral Infection / High Blood Pressure (Hypertension)1
1, 2CompletedTreatmentCraniotomy / High Blood Pressure (Hypertension)1
1, 2CompletedTreatmentMetabolic Syndromes1
2CompletedTreatmentDigital Ulcer of Scleroderma1
2RecruitingTreatmentFlu caused by Influenza1
2, 3CompletedTreatmentHypertrophic Cardiomyopathy1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Heart Diseases / Nonvalvular Atrial Fibrillation1
3CompletedTreatmentCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
3CompletedTreatmentChronic Anal Fissures2
3CompletedTreatmentHeart Failure, Unspecified / High Blood Pressure (Hypertension)1
3CompletedTreatmentNonvalvular Atrial Fibrillation1
3TerminatedTreatmentHeart Failure, Unspecified / Nonvalvular Atrial Fibrillation1
3Unknown StatusTreatmentIschaemia-reperfusion Injury1
3WithdrawnTreatmentDiabetic Nephropathies / High Blood Pressure (Hypertension)1
4CompletedSupportive CarePain NOS1
4CompletedTreatmentAcute Myocardial Infarction (AMI) / Percutaneous Coronary Intervention1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHeart Rate and Rhythm Disorders1
4CompletedTreatmentRapid Ventricular Response Atrial Fibrillation1
4RecruitingTreatmentAcute Ischemic Stroke (AIS)1
4RecruitingTreatmentAtrial Fibrillation and Flutter1
4RecruitingTreatmentAtrial Flutter / Nonvalvular Atrial Fibrillation1
4RecruitingTreatmentFissure in Ano1
4RecruitingTreatmentNonvalvular Atrial Fibrillation / Permanent Atrial Fibrillation1
4Unknown StatusTreatmentNonvalvular Atrial Fibrillation1
Not AvailableActive Not RecruitingTreatmentChronic Anal Fissures1
Not AvailableCompletedDiagnosticCoronary Artery Ectasia1
Not AvailableCompletedTreatmentArrythmias / Nonvalvular Atrial Fibrillation1
Not AvailableTerminatedTreatmentNon-Cardiac Chest Pain1
Not AvailableUnknown StatusTreatmentFamilial Primary Pulmonary Hypertension / Idiopathic Pulmonary Arterial Hypertension / Primary Pulmonary Hypertension / Pulmonary Arterial Hypertension (PAH)1

Pharmacoeconomics

Manufacturers
  • Biovail laboratories inc
  • Watson laboratories inc florida
  • Watson laboratories inc
  • Apotex inc
  • Actavis elizabeth llc
  • Kv pharmaceutical co
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Apotex inc etobicoke site
  • Biovail corp international
  • Biovail laboratories international srl
  • Apotex inc richmond hill
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • International medication systems ltd
  • Taylor pharmacal co
  • Teva parenteral medicines inc
  • Apothecon inc div bristol myers squibb
  • Dava pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Teva pharmaceuticals usa
  • Merck and co inc
Packagers
  • Abbott Laboratories Ltd.
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Akorn Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Biovail Pharmaceuticals
  • Bracco Diagnostics Inc.
  • Bryant Ranch Prepack
  • BTA Pharmaceuticals
  • Cardinal Health
  • Caremark LLC
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Driam Usa Inc.
  • Elan Pharmaceuticals Inc.
  • Ethex Corp.
  • Ethypharm
  • Forest Pharmaceuticals
  • Gruppo Lepetit SPA
  • Heartland Repack Services LLC
  • Hl Moore Drug Exchange
  • Hospira Inc.
  • Inwood Labs
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • KV Pharmaceutical Co.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Long Wing International Inc.
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Meridian Medical Technologies Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neighborcare Repackaging Inc.
  • Neuman Distributors Inc.
  • Novex Pharma
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Pharmedium
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Sanofi-Aventis Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Ther-Rx Corp.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • Vetter Pharma Fertigung GmbH and Co. KG
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
Capsule, extended releaseOral120 mg
Capsule, extended releaseOral180 mg
Capsule, extended releaseOral240 mg
Capsule, extended releaseOral300 mg
Tablet, coatedOral120 mg/1
Tablet, coatedOral30 mg/1
Tablet, coatedOral60 mg/1
Tablet, coatedOral90 mg/1
CapsuleOral120 mg/1
CapsuleOral180 mg/1
CapsuleOral240 mg/1
CapsuleOral300 mg/1
CapsuleOral360 mg/1
Capsule, coated, extended releaseOral360 mg/1
LiquidIntravenous5 mg
TabletOral120 mg/1
TabletOral180 mg/1
TabletOral240 mg/1
TabletOral300 mg/1
TabletOral360 mg/1
TabletOral420 mg/1
Capsule, extended releaseOral60 mg
Capsule, extended releaseOral90 mg
Injection, solutionIntravenous0.83 mg/1mL
Injection, solutionIntravenous1 mg/1mL
Capsule, extended releaseOral120 mg/1
Capsule, extended releaseOral180 mg/1
Capsule, extended releaseOral240 mg/1
Capsule, extended releaseOral300 mg/1
Capsule, extended releaseOral360 mg/1
Capsule, extended releaseOral420 mg/1
Capsule, extended releaseOral60 mg/1
Capsule, extended releaseOral90 mg/1
InjectionIntravenous5 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/1
Injection, solutionIntravenous5 mg/1mL
TabletOral30 mg/1
TabletOral60 mg/1
TabletOral90 mg/1
Tablet, film coatedOral120 mg/1
Tablet, film coatedOral30 mg/1
Tablet, film coatedOral60 mg/1
Tablet, film coatedOral90 mg/1
Capsule, coated, extended releaseOral120 mg/1
Capsule, coated, extended releaseOral180 mg/1
Capsule, coated, extended releaseOral240 mg/1
Capsule, coated, extended releaseOral300 mg/1
Tablet, extended releaseOral120 mg/1
Tablet, extended releaseOral180 mg/1
Tablet, extended releaseOral240 mg/1
Tablet, extended releaseOral300 mg/1
Tablet, extended releaseOral360 mg/1
Tablet, extended releaseOral420 mg/1
SolutionIntravenous5 mg
TabletOral30 mg
TabletOral60 mg
Capsule, extended releaseOral360 mg
Tablet, extended releaseOral120 mg
Tablet, extended releaseOral180 mg
Tablet, extended releaseOral240 mg
Tablet, extended releaseOral300 mg
Tablet, extended releaseOral360 mg
Prices
Unit descriptionCostUnit
Cormax 0.05% Solution 50ml Bottle81.6USD bottle
Cormax 0.05% Solution 25ml Bottle45.99USD bottle
Cormax 0.05% Cream 15 gm Tube43.98USD tube
Diltiazem hcl 100 mg vial9.54USD vial
Diltiazem hcl powder8.42USD g
Cardizem CD 360 mg 24 Hour Capsule7.94USD capsule
Cardizem cd 360 mg capsule7.63USD capsule
Cardizem CD 300 mg 24 Hour Capsule7.3USD capsule
Cardizem LA 420 mg 24 Hour tablet5.56USD tablet
Cardizem CD 240 mg 24 Hour Capsule5.48USD capsule
Cardizem la 420 mg tablet5.35USD tablet
Diltiazem HCl Coated Beads 420 mg 24 Hour tablet5.01USD tablet
Cardizem la 360 mg tablet4.94USD tablet
Cardizem LA 360 mg 24 Hour tablet4.81USD tablet
Cardizem LA 300 mg 24 Hour tablet4.71USD tablet
Diltiazem HCl Coated Beads 360 mg 24 Hour tablet4.62USD tablet
Cardizem la 300 mg tablet4.59USD tablet
Diltiazem HCl Coated Beads 300 mg 24 Hour tablet4.3USD tablet
Cardizem CD 180 mg 24 Hour Capsule3.98USD capsule
Tiazac 420 mg 24 Hour Capsule3.88USD capsule
Tiazac 360 mg 24 Hour Capsule3.7USD capsule
Cardizem LA 240 mg 24 Hour tablet3.67USD tablet
Tiazac 300 mg 24 Hour Capsule3.64USD capsule
Cardizem la 240 mg tablet3.53USD tablet
Cardizem 120 mg tablet3.49USD tablet
Cardizem CD 120 mg 24 Hour Capsule3.4USD capsule
Dilacor XR 180 mg 24 Hour Capsule3.3USD capsule
Dilacor XR 240 mg 24 Hour Capsule3.3USD capsule
Diltiazem HCl Coated Beads 240 mg 24 Hour tablet3.3USD tablet
Dilacor xr 240 mg capsule3.29USD capsule
Cardizem Cd 300 mg Controlled-Delivery Capsule3.25USD capsule
Cardizem la 180 mg tablet3.15USD tablet
Cardizem LA 180 mg 24 Hour tablet3.07USD tablet
Dilacor xr 180 mg capsule3.07USD capsule
Tiazac er 420 mg capsule3.03USD capsule
Cardizem la 120 mg tablet2.98USD tablet
Diltiazem HCl Coated Beads 180 mg 24 Hour tablet2.95USD tablet
Diltiazem HCl ER Beads 420 mg 24 Hour Capsule2.87USD capsule
Dilacor XR 120 mg 24 Hour Capsule2.86USD capsule
Tiazac er 360 mg capsule2.86USD capsule
Tiazac er 300 mg capsule2.83USD capsule
Tiazac 240 mg 24 Hour Capsule2.8USD capsule
Cartia XT 300 mg 24 Hour Capsule2.76USD capsule
Dilt-CD 300 mg 24 Hour Capsule2.76USD capsule
Diltiazem HCl Coated Beads 300 mg 24 Hour Capsule2.76USD capsule
Cormax 0.05% cream2.71USD g
Cartia xt 300 mg capsule2.66USD capsule
Dilt-cd er 300 mg capsule2.66USD capsule
Dilacor xr 120 mg capsule2.61USD capsule
Cardizem Cd 240 mg Controlled-Delivery Capsule2.6USD capsule
Diltiazem HCl ER Beads 360 mg 24 Hour Capsule2.44USD capsule
Tiazac 360 mg Extended-Release Capsule2.42USD capsule
Diltiazem HCl ER Beads 300 mg 24 Hour Capsule2.39USD capsule
Cardizem LA 120 mg 24 Hour tablet2.35USD tablet
Tiazac 240 mg capsule sa2.31USD capsule
Tiazac er 240 mg capsule2.18USD capsule
Cardizem cd 300 mg capsule2.15USD capsule
Cartia XT 240 mg 24 Hour Capsule2.13USD capsule
Diltiazem HCl Coated Beads 240 mg 24 Hour Capsule2.13USD capsule
Dilt-cd 240 mg capsule2.05USD capsule
Cardizem 90 mg tablet2.02USD tablet
Tiazac 180 mg 24 Hour Capsule1.98USD capsule
Tiazac 300 mg Extended-Release Capsule1.98USD capsule
Cardizem Cd 180 mg Controlled-Delivery Capsule1.96USD capsule
Diltiazem HCl ER Beads 240 mg 24 Hour Capsule1.85USD capsule
Cardizem sr 120 mg capsule1.83USD capsule
Apo-Diltiaz Cd 300 mg Controlled-Delivery Capsule1.82USD capsule
Novo-Diltazem Cd 300 mg Controlled-Delivery Capsule1.82USD capsule
Ratio-Diltiazem Cd 300 mg Controlled-Delivery Capsule1.82USD capsule
Sandoz Diltiazem Cd 300 mg Controlled-Delivery Capsule1.82USD capsule
Cardizem cd 240 mg capsule1.69USD capsule
Tiazac 120 mg 24 Hour Capsule1.69USD capsule
Tiazac 240 mg Extended-Release Capsule1.61USD capsule
Tiazac er 180 mg capsule1.52USD capsule
Cartia XT 180 mg 24 Hour Capsule1.5USD capsule
Dilt-CD 180 mg 24 Hour Capsule1.5USD capsule
Diltiazem HCl Coated Beads 180 mg 24 Hour Capsule1.5USD capsule
Cardizem Cd 120 mg Controlled-Delivery Capsule1.48USD capsule
Apo-Diltiaz Cd 240 mg Controlled-Delivery Capsule1.46USD capsule
Novo-Diltazem Cd 240 mg Controlled-Delivery Capsule1.46USD capsule
Nu-Diltiaz-Cd 240 mg Controlled-Delivery Capsule1.46USD capsule
Ratio-Diltiazem Cd 240 mg Controlled-Delivery Capsule1.46USD capsule
Sandoz Diltiazem Cd 240 mg Controlled-Delivery Capsule1.46USD capsule
Tiazac Xc 240 mg Extended-Release Tablet1.46USD tablet
Tiazac Xc 300 mg Extended-Release Tablet1.46USD tablet
Tiazac Xc 360 mg Extended-Release Tablet1.46USD tablet
Dilt-cd 180 mg capsule1.45USD capsule
Diltiazem HCl 120 mg tablet1.42USD tablet
Diltiazem 120 mg tablet1.36USD tablet
Apo-Diltiaz Tz 360 mg Extended-Release Capsule1.36USD capsule
Novo-Diltiazem Hcl Er 360 mg Extended-Release Capsule1.36USD capsule
Sandoz Diltiazem T 360 mg Extended-Release Capsule1.36USD capsule
Cardizem 30 mg tablet1.34USD tablet
Diltiazem HCl ER Beads 180 mg 24 Hour Capsule1.3USD capsule
Diltiazem HCl CR 120 mg 12 Hour Capsule1.29USD capsule
Tiazac er 120 mg capsule1.26USD capsule
Cartia XT 120 mg 24 Hour Capsule1.25USD capsule
Dilt-CD 120 mg 24 Hour Capsule1.25USD capsule
Diltiazem HCl Coated Beads 120 mg 24 Hour Capsule1.25USD capsule
Cardizem cd 180 mg capsule1.24USD capsule
Tiazac 180 mg Extended-Release Capsule1.21USD capsule
Cartia xt 120 mg capsule1.2USD capsule
Dilt-cd 120 mg capsule1.2USD capsule
Diltiazem HCl CR 240 mg 24 Hour Capsule1.19USD capsule
Diltia XT 240 mg 24 Hour Capsule1.17USD capsule
Diltiazem HCl CR 180 mg 24 Hour Capsule1.11USD capsule
Apo-Diltiaz Tz 300 mg Extended-Release Capsule1.11USD capsule
Novo-Diltiazem Hcl Er 300 mg Extended-Release Capsule1.11USD capsule
Sandoz Diltiazem T 300 mg Extended-Release Capsule1.11USD capsule
Tiazac Xc 180 mg Extended-Release Tablet1.1USD tablet
Diltia XT 180 mg 24 Hour Capsule1.1USD capsule
Apo-Diltiaz Cd 180 mg Controlled-Delivery Capsule1.1USD capsule
Novo-Diltazem Cd 180 mg Controlled-Delivery Capsule1.1USD capsule
Nu-Diltiaz-Cd 180 mg Controlled-Delivery Capsule1.1USD capsule
Ratio-Diltiazem Cd 180 mg Controlled-Delivery Capsule1.1USD capsule
Sandoz Diltiazem Cd 180 mg Controlled-Delivery Capsule1.1USD capsule
Diltiazem HCl ER Beads 120 mg 24 Hour Capsule1.08USD capsule
Diltiazem HCl 90 mg tablet1.05USD tablet
Diltiazem 90 mg tablet1.01USD tablet
Diltiazem HCl CR 90 mg 12 Hour Capsule0.99USD capsule
Cardizem cd 120 mg capsule0.97USD capsule
Cardizem 60 mg tablet0.95USD tablet
Diltiazem HCl CR 120 mg 24 Hour Capsule0.95USD capsule
Apo-Diltiaz Tz 240 mg Extended-Release Capsule0.9USD capsule
Novo-Diltiazem Hcl Er 240 mg Extended-Release Capsule0.9USD capsule
Sandoz Diltiazem T 240 mg Extended-Release Capsule0.9USD capsule
Tiazac 120 mg Extended-Release Capsule0.89USD capsule
Diltiazem HCl CR 60 mg 12 Hour Capsule0.86USD capsule
Apo-Diltiaz Cd 120 mg Controlled-Delivery Capsule0.83USD capsule
Novo-Diltazem Cd 120 mg Controlled-Delivery Capsule0.83USD capsule
Nu-Diltiaz-Cd 120 mg Controlled-Delivery Capsule0.83USD capsule
Ratio-Diltiazem Cd 120 mg Controlled-Delivery Capsule0.83USD capsule
Sandoz Diltiazem Cd 120 mg Controlled-Delivery Capsule0.83USD capsule
Tiazac Xc 120 mg Extended-Release Tablet0.83USD tablet
Cartia xt 240 mg capsule0.81USD capsule
Diltiazem HCl 60 mg tablet0.77USD tablet
Diltiazem 60 mg tablet0.74USD tablet
Apo-Diltiaz Tz 180 mg Extended-Release Capsule0.68USD capsule
Novo-Diltiazem Hcl Er 180 mg Extended-Release Capsule0.68USD capsule
Sandoz Diltiazem T 180 mg Extended-Release Capsule0.68USD capsule
Cartia xt 180 mg capsule0.6USD capsule
Apo-Diltiaz Tz 120 mg Extended-Release Capsule0.5USD capsule
Novo-Diltiazem Hcl Er 120 mg Extended-Release Capsule0.5USD capsule
Sandoz Diltiazem T 120 mg Extended-Release Capsule0.5USD capsule
Diltiazem HCl 30 mg tablet0.49USD tablet
Diltiazem 30 mg tablet0.47USD tablet
Diltia xt 240 mg capsule0.43USD capsule
Diltia xt 180 mg capsule0.42USD capsule
Diltiazem-d5w 250 mg/250 ml0.42USD ml
Diltia xt 120 mg capsule0.38USD capsule
Apo-Diltiaz 60 mg Tablet0.38USD tablet
Novo-Diltazem 60 mg Tablet0.38USD tablet
Nu-Diltiaz 60 mg Tablet0.38USD tablet
Apo-Diltiaz 30 mg Tablet0.22USD tablet
Novo-Diltazem 30 mg Tablet0.22USD tablet
Nu-Diltiaz 30 mg Tablet0.22USD tablet
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Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5286497No1994-02-152011-05-20Us
CA2307547No2007-08-142020-05-04Canada
CA2111085No1999-04-272012-06-25Canada
US7108866No2006-09-192019-12-17Us
US6923984No2005-08-022021-02-25Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)187-188Kugita, H., Inoue, H., Ikezaki, M. and Takeo, S.; U.S. Patent 3,562,257; assigned to Tanabe Seiyaku Co.,Ltd., Japan.
water solubility465 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP2.8Not Available
Caco2 permeability-4.38ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0168 mg/mLALOGPS
logP3.09ALOGPS
logP2.73ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)12.86ChemAxon
pKa (Strongest Basic)8.18ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area59.08 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity114.37 m3·mol-1ChemAxon
Polarizability43.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9788
Blood Brain Barrier+0.506
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.8645
P-glycoprotein inhibitor IInhibitor0.8675
P-glycoprotein inhibitor IIInhibitor0.8997
Renal organic cation transporterNon-inhibitor0.7634
CYP450 2C9 substrateNon-substrate0.699
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8681
Ames testNon AMES toxic0.6985
CarcinogenicityNon-carcinogens0.8772
BiodegradationNot ready biodegradable0.9951
Rat acute toxicity2.4130 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9971
hERG inhibition (predictor II)Inhibitor0.7723
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
Mass Spectrum (Electron Ionization)MSsplash10-0ab9-9200000000-b1095b8fe5973d23fdd6
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzothiazepines. These are organic compounds containing a benzene fused to a thiazepine ring (a seven-membered ring with a nitrogen atom and a sulfur atom replacing two carbon atoms).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazepines
Sub Class
Not Available
Direct Parent
Benzothiazepines
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Alkylarylthioethers / Tertiary carboxylic acid amides / Trialkylamines / Amino acids and derivatives / Lactams / Carboxylic acid esters
show 6 more
Substituents
Benzothiazepine / Phenoxy compound / Aryl thioether / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Alkylarylthioether / Monocyclic benzene moiety / Benzenoid
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate (CHEBI:101278)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only...
Gene Name
CACNG1
Uniprot ID
Q06432
Uniprot Name
Voltage-dependent calcium channel gamma-1 subunit
Molecular Weight
25028.105 Da
References
  1. Budriesi R, Ioan P, Carosati E, Cruciani G, Zhorov BS, Chiarini A: Ligands of diltiazem binding site: an overview of some chemotypes. Mini Rev Med Chem. 2009 Oct;9(12):1379-88. [PubMed:19929811]
  2. Romero M, Sanchez I, Pujol MD: New advances in the field of calcium channel antagonists: cardiovascular effects and structure-activity relationships. Curr Med Chem Cardiovasc Hematol Agents. 2003 Jun;1(2):113-41. [PubMed:15320693]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [PubMed:12124305]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  2. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Kosuge K, Jun Y, Watanabe H, Kimura M, Nishimoto M, Ishizaki T, Ohashi K: Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Drug Metab Dispos. 2001 Oct;29(10):1284-9. [PubMed:11560871]
  2. McGinnity DF, Parker AJ, Soars M, Riley RJ: Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metab Dispos. 2000 Nov;28(11):1327-34. [PubMed:11038161]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Molden E, Asberg A, Christensen H: Desacetyl-diltiazem displays severalfold higher affinity to CYP2D6 compared with CYP3A4. Drug Metab Dispos. 2002 Jan;30(1):1-3. [PubMed:11744603]
  3. Molden E, Johansen PW, Boe GH, Bergan S, Christensen H, Rugstad HE, Rootwelt H, Reubsaet L, Lehne G: Pharmacokinetics of diltiazem and its metabolites in relation to CYP2D6 genotype. Clin Pharmacol Ther. 2002 Sep;72(3):333-42. doi: 10.1067/mcp.2002.127396. [PubMed:12235455]
  4. Molden E, Asberg A, Christensen H: CYP2D6 is involved in O-demethylation of diltiazem. An in vitro study with transfected human liver cells. Eur J Clin Pharmacol. 2000 Nov;56(8):575-9. [PubMed:11151747]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
  2. Takara K, Sakaeda T, Tanigawara Y, Nishiguchi K, Ohmoto N, Horinouchi M, Komada F, Ohnishi N, Yokoyama T, Okumura K: Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression. Eur J Pharm Sci. 2002 Aug;16(3):159-65. [PubMed:12128170]
  3. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T: P-glycoprotein-mediated transcellular transport of MDR-reversing agents. FEBS Lett. 1993 Jun 7;324(1):99-102. [PubMed:8099333]

Drug created on June 13, 2005 07:24 / Updated on November 17, 2018 07:07