Identification

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

Diltiazem is a benzothiazepine derivative with antihypertensive and vasodilating properties. Approved in 1982 by the FDA, it is a member of the non-dihydropyridine calcium channel blockers drug class. It works through various mechanisms of action, but it primarily works by inhibiting the calcium influx into cardiac and vascular smooth muscle during depolarization.Label Compared to dihydropyridine drugs, such as nifedipine, that preferentially act on vascular smooth muscle and verapamil that directly acts on the heart muscle, diltiazem displays an intermediate specificity to target both the cardiac and vascular smooth muscle.7 Being a potent vasodilator, diltiazem is used clinically as an antihypertensive, anti-arrhythmic, and as an anti-anginal agent8 for the management of cardiovascular conditions such as hypertension, chronic stable angina, atrial fibrillation, atrial flutter. Apart from its main FDA-approved indications, diltiazem has also been used for numerous off-label indications, such as anal fissures (in topical formulations), migraine prophylaxis, pulmonary hypertension, and rest-related cramps in the lower extremities.8 Typically available in extended-release oral and intravenous formulations, diltiazem is marketed under various brand names with Cardizem and Tiazac being the most common ones.

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 releaseOralTEVA Canada Limited2011-10-06Not applicableCanada
Act Diltiazem CDCapsule, extended releaseOralTEVA Canada Limited2011-10-06Not applicableCanada
Act Diltiazem CDCapsule, extended releaseOralTEVA Canada Limited2011-10-06Not applicableCanada
Act Diltiazem CDCapsule, extended releaseOralTEVA Canada Limited2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended releaseOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended releaseOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended releaseOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended releaseOralActavis Pharma Company2011-10-06Not applicableCanada
Act Diltiazem TCapsule, extended releaseOralActavis Pharma Company2011-10-06Not applicableCanada
CardizemTablet, coated60 mg/1OralValeant Pharmaceuticals North America LLC2010-12-25Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alti-diltiazem Tab 30mgTabletOralAltimed Pharma Inc.1990-12-312005-05-27Canada
Alti-diltiazem Tab 60mgTabletOralAltimed Pharma Inc.1990-12-312005-05-27Canada
Apo-diltiazTabletOralApotex Corporation1988-12-31Not applicableCanada
Apo-diltiazTabletOralApotex Corporation1988-12-31Not applicableCanada
Apo-diltiaz CDCapsule, extended releaseOralApotex Corporation1997-03-27Not applicableCanada
Apo-diltiaz CDCapsule, extended releaseOralApotex Corporation1996-09-12Not applicableCanada
Apo-diltiaz CDCapsule, extended releaseOralApotex Corporation1997-03-27Not applicableCanada
Apo-diltiaz CDCapsule, extended releaseOralApotex Corporation1997-03-27Not applicableCanada
Apo-diltiaz InjectableLiquidIntravenousApotex Corporation2000-06-202013-08-02Canada
Apo-diltiaz SRCapsule, extended releaseOralApotex Corporation1996-09-192019-01-16Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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) / 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

Oral

Indicated for the management of hypertension, to lower blood pressure, alone or in combination with other antihypertensive agents.Label

Indicated for use to improve exercise tolerance in patients with chronic stable angina.Label

Indicated for the management of variant angina (Prinzmetal's angina).10

Intravenous

Indicated for the short-term management of atrial fibrillation or atrial flutter for temporary control of rapid ventricular rate.9

Indicated for the rapid conversion of paroxysmal supraventricular tachycardias (PSVT) to sinus rhythm. This includes AV nodal reentrant tachycardias and reciprocating tachycardias associated with an extranodal accessory pathway such as the WPW syndrome or short PR syndrome.9

Off-label

Indicated for off-label uses in anal fissures (as topical formulation), migraine prophylaxis, cramps in lower leg related to rest, pulmonary hypertension,8 idiopathic dilated cardiomyopathy, and proteinuria associated with diabetic nephropathy.10

Associated Conditions
Pharmacodynamics

Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.Label Diltiazem inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Diltiazem is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate).8 It is also considered a rate-control drug as it reduces heart rate.2,7 Diltiazem is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow.9 Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations.Label In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.9

As the magnitude of blood pressure reduction is related to the degree of hypertension, the antihypertensive effect of diltiazem is most pronounced in individuals with hypertension.Label In a randomized, double-blind, parallel-group, dose-response study involving patients with essential hypertension, there was a reduction in the diastolic blood pressure by 1.9, 5.4, 6.1, and 8.6 mmHg in the patients receiving diltiazem at doses of 120, 240, 360, and 540 mg, respectively. In patients receiving placebo, there was a reduction in the diastolic blood pressure by 2.6 mmHg.Label In a randomized, double-blind study involving patients with chronic stable angina, variable doses of diltiazem administered at night all caused an increased exercise tolerance in the after 21 hours, compared to placebo.Label In the NORDIL study of patients with hypertension, the therapeutic effectiveness of diltiazem in reducing cardiovascular morbidity and mortality was assessed.2 When using the combined primary endpoint as fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death, fatal and non-fatal stroke was shown to be reduced by 25% in the diltiazem group. Although the clinical significance to this effect remains unclear, it is suggested that diltiazem may exert a protective role against cerebral stroke in hypertensive patients.2

Mechanism of action

Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channels3 associated with a high activation threshold and slow inactivation profile.7 L-type calcium channels are the main current responsible for the late phase of the pacemaker potential.5 Acting as the main Ca2+ source for contraction in smooth and cardiac muscle, activation of L-type calcium channels allows the influx of calcium ions into the muscles upon depolarization and excitation of the channel.3 It is proposed that this cation influx may also trigger the release of additional calcium ions from intracellular storage sites.3 Diltiazem is a slow calcium channel blocker that binds to the extracellular site of the alpha-1C subunit of the channel, which is thought to be the S5-6 linker region of the transmembrane domain IV and/or S6 segment of domain III.5 Diltiazem can get access to this binding site from either the intracellular or extracellular side, but it requires a voltage-induced conformational changes in the membrane.5 Diltiazem inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes.Label In isolated human atrial and ventricular myocardium, diltiazem suppressed tension over the range of membrane potentials associated with calcium channel activity but had little effect on the tension-voltage relations at more positive potentials.4 This effect is thought to be mediated by the voltage-dependent block of the L-type calcium channels and inhibition of calcium ion release from the ER stores, without altering the sodium-calcium coupled transport or calcium sensitivity of myofilaments.4 Through inhibition of inward calcium current, diltiazem exerts a direct ionotropic and energy sparing effect on the myocardium.3 Diltiazem fslows atrioventricular nodal conduction, which is due to its ability to impede slow channel function.3

Reduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and therefore, decreased blood pressure.8 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.Label,8 Through its actions on reducing calcium levels in cardiac and vascular smooth muscles, diltiazem causes a reduction in the contractile processes of the myocardial smooth muscle cells and vasodilation of the coronary and systemic arteries, including epicardial and subendocardial. This subsequently leads to increased oxygen delivery to the myocardial tissue, improved cardiac output due to increased stroke volume, decreased total peripheral resistance, decreased systemic blood pressure and heart rate, and decreased afterload.Label,8 Diltiazem lowers myocardial oxygen demand through a reduction in heart rate, blood pressure, and cardiac contractility; this leads to a therapeutic effect in improving exercise tolerance in chronic stable angina.2,8

TargetActionsOrganism
AVoltage-dependent calcium channel gamma-1 subunit
blocker
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1C
blocker
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Absorption

Diltiazem is readily absorbed from the gastrointestinal tract. Minimum therapeutic plasma diltiazem concentrations appear to be in the range of 50 to 200 ng/mL.Label Following oral administration of extended formulations of 360 mg diltiazem, the drug in plasma was detectable within 3 to 4 hours and the peak plasma concentrations were reached between 11 and 18 hours post-dose. Diltiazem peak and systemic exposures were not affected by concurrent food intake.Label Due to hepatic first-pass metabolism, the absolute bioavailability following oral administration is about 40%Label, with the value ranging from 24 to 74% due to high interindividual variation in the first pass effect.1 The bioavailability may increase in patients with hepatic impairment.Label

Volume of distribution

The apparent volume of distribution of diltiazem was approximately 305 L following a single intravenous injection in healthy male volunteers.9

Protein binding

Diltiazem is about 70-80% bound to plasma proteins, according to in vitro binding studies.Label About 40% of the drug is thought to bind to alpha-1-glycoprotein at clinically significant concentrations while about 30% of the drug is bound to albumin.9

Metabolism

Diltiazem is subject to extensive first-pass metabolism, which explains its relatively low absolute oral bioavailability. It undergoes metabolism primarily mediated by CYP3A4. Diltiazem is reported to undergo deacetylation, N- demethylation, and O-demethylation, as well as conjugation reactions mediated by CYP450 enzymes, with CYP3A4 being the primary enzyme responsible for drug metabolism. Metabolites N-monodesmethyldiltiazem, desacetyldiltiazem, desacetyl-N-monodesmethyldiltiazem, desacetyl-O- desmethyldiltiazem, and desacetyl-N, O-desmethyldiltiazem have been identified in human urine.9 It is proposed that N-desmethyldiltiazem, deacetyldiltiazem, deacetyl-N-monodesmethyldiltiazem, and desacetyl-O- desmethyldiltiazem all retain pharmacological activity with varying potency.6 Desacetyldiltiazem is present in the plasma at levels of 10% to 20% of the parent drug and retains about 25-50% of the pharmacological activity to that of the parent compound.Label Radioactivity studies indicate the presence of other metabolites that persist in the plasma for 20 hours, compared to diltiazem that is detectable for 2 to 5 hours.Label

Route of elimination

Due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine.Label

Half life

The plasma elimination half-life is approximately 3.0 - 4.5 hours following single and multiple oral doses. The half-life may slightly increase with dose and the extent of hepatic impairment.Label The apparent elimination half-life for diltiazem as extended-release tablets after single or multiple dosing is 6 to 9 hours.Label The plasma elimination half-life is approximately 3.4 hours following administration of a single intravenous injection.9

Clearance

Following a single intravenous injection in healthy male volunteers, the systemic clearance of diltiazem was approximately 65 L/h. After constant rate intravenous infusion, the systemic clearance decreased to 48 L/h.9

Toxicity

Clinical Toxicity and Overdose

The oral LD50 ranges from 415 to 740mg/kg in mice and 560 to 810 mg/kg in rats. The oral LD50 in dogs is considered to be in excess of 50 mg/kg. A dose of 360 mg/kg resulted in lethality in monkeys. The intravenous LD50 is 60 mg/kg in mice and 38 mg/kg in rats.

Cases of overdose from doses ranging from less than 1 g to 18 g have been reported with diltiazem, with several cases involving multiple drug ingestions resulting in death. Overdoses were associated with bradycardia, hypotension, heart block, and cardiac failure that may manifest as dizziness, lightheadedness, and fatigue.8 Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician. Diltiazem overdose should be responded with appropriate supportive measures and gastrointestinal decontamination. Bradycardia and heart block can be treated with atropine at doses ranging from 0.60 to 1.0 mg. In the case of bradycardia, if there is no response to vagal blockage, cautious administration of isoproterenol should be considered. Cardiac pacing can also be used to treat fixed high-degree AV block. In the case of heart failure, blood pressure may be maintained with the use of fluids and vasopressors, as well as inotropic agents such as isoproterenol, dopamine, or dobutamine. Other appropriate measures include ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. Diltiazem does not appear to be removed by peritoneal or hemodialysis.Label

Non-clinical toxicity

In a 24-month study in rats receiving oral doses of up to 100 mg/kg/day, there was no evidence of carcinogenicity. There was also no mutagenic response in vitro or in vivo in mammalian cell assays or in vitro bacterial assays. No evidence of impaired fertility was observed in a study performed in male and female rats receiving oral doses of up to 100 mg/kg/day.Label

Pregnancy and Lactation

In reproduction studies in animals, administration of diltiazem at doses ranging from five to twenty times the daily recommended human therapeutic dose resulted in cases of the embryo and fetal lethality and skeletal abnormalities, and an increase in the risk of stillbirths. There have been no up-to-date controlled studies that investigated the use of diltiazem in pregnant women. The use of diltiazem in pregnant women should be undertaken only if the potential benefit justifies the risk to the fetus.Label Diltiazem is excreted in human milk, where one report suggests that the concentrations in breast milk may approximate serum levels; therefore, the decision should be made to either discontinue nursing or the use of the drug after careful consideration of the clinical necessity of diltiazem therapy in the nursing mother.Label

Use in special populations

As there is limited information on the variable effects of diltiazem in geriatric patients, the initial therapy of diltiazem should involve the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Currently, there are no specific dosing guidelines for patients with renal or hepatic impairment.Label

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
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
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Diltiazem.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Diltiazem.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Diltiazem can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Diltiazem.
1-benzylimidazole1-benzylimidazole may decrease the antihypertensive activities of Diltiazem.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Diltiazem is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Diltiazem.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Diltiazem.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Diltiazem.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Diltiazem.
Additional Data Available
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    Extended Description

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  • Severity
    Severity

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  • Action
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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
  1. Hermann P, Rodger SD, Remones G, Thenot JP, London DR, Morselli PL: Pharmacokinetics of diltiazem after intravenous and oral administration. Eur J Clin Pharmacol. 1983;24(3):349-52. [PubMed:6861848]
  2. Rodriguez Padial L, Baron-Esquivias G, Hernandez Madrid A, Marzal Martin D, Pallares-Carratala V, de la Sierra A: Clinical Experience with Diltiazem in the Treatment of Cardiovascular Diseases. Cardiol Ther. 2016 Jun;5(1):75-82. doi: 10.1007/s40119-016-0059-1. Epub 2016 Mar 25. [PubMed:27016085]
  3. Nayler WG, Dillon JS: Calcium antagonists and their mode of action: an historical overview. Br J Clin Pharmacol. 1986;21 Suppl 2:97S-107S. doi: 10.1111/j.1365-2125.1986.tb02859.x. [PubMed:3019374]
  4. Sutton MS, Morad M: Mechanisms of action of diltiazem in isolated human atrial and ventricular myocardium. J Mol Cell Cardiol. 1987 May;19(5):497-508. [PubMed:3498047]
  5. O'Connor SE, Grosset A, Janiak P: The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem. Fundam Clin Pharmacol. 1999;13(2):145-53. [PubMed:10226758]
  6. Yeung PK, Prescott C, Haddad C, Montague TJ, McGregor C, Quilliam MA, Xei M, Li R, Farmer P, Klassen GA: Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. Eur J Drug Metab Pharmacokinet. 1993 Apr-Jun;18(2):199-206. doi: 10.1007/BF03188796. [PubMed:8243504]
  7. 4, 22. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 50, 272). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  8. Diltiazem - StatPearls - NCBI Bookshelf [Link]
  9. Diltiazem Hydrochloride Injection Label - Bedford Laboratories [Link]
  10. Cardizem (diltiazem hydrochloride) Drug Summary - PDR.net [Link]
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
HET
C9F
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Diltiazem
ATC Codes
C08DB01 — DiltiazemC05AE03 — Diltiazem
AHFS Codes
  • 24:28.92 — Miscellaneous Calcium-channel Blocking Agents
PDB Entries
6jpb
FDA label
Download (336 KB)
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedScreeningAdenomatous Polyp of Colon / Colorectal Cancers / Neoplasms, Colorectal1
0Not Yet RecruitingPreventionInduction of intra-operative hypotension1
1CompletedNot AvailableNonvalvular Atrial Fibrillation1
1CompletedNot AvailableSubstance, Addiction1
1CompletedBasic ScienceDrug Induced Constipation1
1CompletedBasic ScienceDrug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedBasic ScienceHealthy Volunteers / Pharmacologic Actions1
1CompletedBasic ScienceHealthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein1
1CompletedBasic ScienceOpioid Dependence1
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 / High Blood Pressure (Hypertension)1
3CompletedTreatmentNonvalvular Atrial Fibrillation1
3TerminatedTreatmentHeart Failure / Nonvalvular Atrial Fibrillation1
3Unknown StatusTreatmentIschaemia-reperfusion Injury1
3WithdrawnTreatmentDiabetic Nephropathies / High Blood Pressure (Hypertension)1
4CompletedNot AvailableHealthy Volunteers1
4CompletedSupportive CarePain NOS1
4CompletedTreatmentAcute Coronary Syndromes (ACS)1
4CompletedTreatmentAcute Myocardial Infarction (AMI) / Percutaneous Coronary Intervention1
4CompletedTreatmentArteriospasm coronary1
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
4Unknown StatusTreatmentStable Angina (SA)1
Not AvailableActive Not RecruitingTreatmentChronic Anal Fissures1
Not AvailableCompletedNot AvailableHeart Failure / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedDiagnosticCoronary Artery Ectasia1
Not AvailableCompletedTreatmentArrythmias / Nonvalvular Atrial Fibrillation1
Not AvailableTerminatedTreatmentNon-Cardiac Chest Pain1
Not AvailableWithdrawnTreatmentFamilial 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
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  • Vetter Pharma Fertigung GmbH and Co. KG
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
LiquidIntravenous
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
Capsule, extended releaseOral120 mg
Capsule, extended releaseOral180 mg
Capsule, extended releaseOral240 mg
Capsule, extended releaseOral300 mg
TabletOral120 mg/1
TabletOral180 mg/1
TabletOral240 mg/1
TabletOral300 mg/1
TabletOral360 mg/1
TabletOral420 mg/1
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
SolutionIntravenous
TabletOral
Capsule, extended releaseOral
Tablet, extended releaseOral
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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
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
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

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/LMCFARLAND,JW ET AL. (2001)
logP2.8Human Metabolome Database (HMDB)
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
Humans
Pharmacological action
Yes
Actions
Blocker
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]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Blocker
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight
248974.1 Da
References
  1. O'Connor SE, Grosset A, Janiak P: The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem. Fundam Clin Pharmacol. 1999;13(2):145-53. [PubMed:10226758]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
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. 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]
  2. 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]
  3. Flockhart Table of Drug Interactions [Link]
  4. Drug Interactions & Labeling - FDA [Link]
  5. Co-Administration of the CYP3A4 Inhibitor Diltiazem Counteracts Mitotane-Induced Clearance of Glucocorticoids and Antihypertensives in a Patient with Adrenocortical Carcinoma [Link]
Kind
Protein
Organism
Humans
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. Yamamoto T, Kubota T, Ozeki T, Sawada M, Yokota S, Yamada Y, Kumagai Y, Iga T: Effects of the CYP3A5 genetic polymorphism on the pharmacokinetics of diltiazem. Clin Chim Acta. 2005 Dec;362(1-2):147-54. doi: 10.1016/j.cccn.2005.06.013. Epub 2005 Jul 15. [PubMed:16024008]
  2. Zheng T, Su CH, Zhao J, Zhang XJ, Zhang TY, Zhang LR, Kan QC, Zhang SJ: Effects of CYP3A5 and CYP2D6 genetic polymorphism on the pharmacokinetics of diltiazem and its metabolites in Chinese subjects. Pharmazie. 2013 Apr;68(4):257-60. [PubMed:23700791]
  3. Zhou LY, Zuo XC, Chen K, Wang JL, Chen QJ, Zhou YN, Yuan H, Ma Y, Zhu LJ, Peng YX, Ming YZ: Significant impacts of CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the pharmacokinetics of diltiazem and its main metabolites in Chinese adult kidney transplant patients. J Clin Pharm Ther. 2016 Jun;41(3):341-7. doi: 10.1111/jcpt.12394. Epub 2016 May 5. [PubMed:27149910]
  4. Pinto AG, Horlander J, Chalasani N, Hamman M, Asghar A, Kolwankar D, Hall SD: Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein. Br J Clin Pharmacol. 2005 Apr;59(4):440-6. doi: 10.1111/j.1365-2125.2005.02343.x. [PubMed:15801939]
  5. Flockhart Table of Drug Interactions [Link]
  6. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Humans
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. Flockhart Table of Drug Interactions [Link]
  2. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Humans
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
Humans
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. 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]
  2. 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]
  3. 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
Humans
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. Sutton D, Butler AM, Nadin L, Murray M: Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. J Pharmacol Exp Ther. 1997 Jul;282(1):294-300. [PubMed:9223567]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Diltiazem Hydrochloride Injection Label - Bedford Laboratories [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Diltiazem Hydrochloride Injection Label - Bedford Laboratories [Link]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
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 October 18, 2019 21:36