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| Mechanism of Action |
Diltiazem¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, dilitiazem, 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.
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| Pharmacology |
Diltiazem¿¡ ´ëÇÑ Pharmacology Á¤º¸ 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 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.
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| Metabolism |
Diltiazem¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2C19 (CYP2C19)Cytochrome P450 2D6 (CYP2D6)
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| Protein Binding |
Diltiazem¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 70%-80%
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| Half-life |
Diltiazem¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3.0 - 4.5 hours
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| Absorption |
Diltiazem¿¡ ´ëÇÑ Absorption Á¤º¸ Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.
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| Pharmacokinetics |
Diltiazem HClÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
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- ºÐÆ÷ : Vd 1.7 L/kg. À¯ÁóÀ¸·Îµµ ºÐÆ÷ÇÑ´Ù.
- ´Ü¹é°áÇÕ : 77-85%
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| Biotransformation |
Diltiazem¿¡ ´ëÇÑ Biotransformation Á¤º¸ Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.
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| Toxicity |
Diltiazem¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50=740mg/kg (orally in mice)
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| Drug Interactions |
Diltiazem¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amiodarone Increased risk of cardiotoxicity and arrhythmiasAmlodipine Increases the effect and toxicity of amlodipineAprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitantAtazanavir Atazanavir increases the effect and toxicity of diltiazemAtenolol Increased risk of bradycardiaAtorvastatin Increases the effect and toxicity of atorvastatinBuspirone The calcium channel blocker increases the effect and toxicity of buspironeCarbamazepine Increases the effect of carbamazepineCerivastatin Increases the effect and toxicity of the statinCilostazol Increases the effect of cilostazolCisapride Increases the levels of cisaprideCyclosporine Increases the effect and toxicity of cyclosporineDihydroquinidine barbiturate Increases the effect and toxicity of quinidineLovastatin Increases the effect and toxicity of the statinMesoridazine Increased risk of cardiotoxicity and arrhythmiasMetoprolol Increased risk of bradycardiaMidazolam The calcium channel blocker increases the effect and toxicity of the benzodiazepineMoricizine Increased effect/toxicity of moricizinePindolol Increased risk of bradycardiaPropranolol Increased risk of bradycardiaQuinidine Increases the effect and toxicity of quinidineQuinidine barbiturate Increases the effect and toxicity of quinidineQuinupristin This combination presents an increased risk of toxicityRanolazine Increased levels of ranolazine- risk of toxicityRifampin Rifampin decreases levels of diltiazemRitonavir Ritonavir increases diltiazem levelsSimvastatin Increases the effect and toicity of simvastatinSirolimus Increases the effect and toxicity of sirolimusTacrolimus Increases levels of tacrolimusTerfenadine Increased risk of cardiotoxicity and arrhythmiasThioridazine Increased risk of cardiotoxicity and arrhythmiasTriazolam The calcium channel blocker increases the effect and toxicity of the benzodiazepine
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸] Diltiazem¿¡ ´ëÇÑ P450 table
SUBSTRATES
CYP 3A4/3A5/3A7
Macrolide antibiotics:
clarithromycin
erythromycin
NOT azithromycin
telithromycin
Anti-arrhythmics:
quinidine
Benzodiazepines:
alprazolam
diazepam
midazolam
triazolam
Immune Modulators:
cyclosporine
tacrolimus (FK506)
HIV Protease Inhibitors:
indinavir
ritonavir
saquinavir
Prokinetic:
cisapride
Antihistamines:
astemizole
chlorpheniramine
Calcium Channel Blockers:
amlodipine
**diltiazem**
felodipine
nifedipine
nisoldipine
nitrendipine
verapamil
HMG CoA Reductase Inhibitors:
atorvastatin
cerivastatin
lovastatin
NOT pravastatin
simvastatin
aripiprazole
buspirone
gleevec
haloperidol (in part)
methadone
pimozide
quinine
NOT rosuvastatin
sildenafil
tamoxifen
trazodone
vincristine
INHIBITORS
CYP 3A4/3A5/3A7
HIV Protease Inhibitors:
indinavir
nelfinavir
ritonavir
amiodarone
NOT azithromycin
cimetidine
clarithromycin
**diltiazem**
erythromycin
fluvoxamine
grapefruit juice
itraconazole
ketoconazole
mibefradil
nefazodone
troleandomycin
verapamil
INDUCERS
CYP 3A4/3A5/3A7
carbamazepine
phenobarbital
phenytoin
rifabutin
rifampin
St. John's wort
troglitazone
SUBSTRATES
CYP 3A4/3A5/3A7
Macrolide antibiotics:
clarithromycin
erythromycin
NOT azithromycin
telithromycin
Anti-arrhythmics:
quinidine
Benzodiazepines:
alprazolam
diazepam
midazolam
triazolam
Immune Modulators:
cyclosporine
tacrolimus (FK506)
HIV Protease Inhibitors:
indinavir
ritonavir
saquinavir
Prokinetic:
cisapride
Antihistamines:
astemizole
chlorpheniramine
Calcium Channel Blockers:
amlodipine
**diltiazem**
felodipine
nifedipine
nisoldipine
nitrendipine
verapamil
HMG CoA Reductase Inhibitors:
atorvastatin
cerivastatin
lovastatin
NOT pravastatin
simvastatin
aripiprazole
buspirone
gleevec
haloperidol (in part)
methadone
pimozide
quinine
NOT rosuvastatin
sildenafil
tamoxifen
trazodone
vincristine
INHIBITORS
CYP 3A4/3A5/3A7
HIV Protease Inhibitors:
indinavir
nelfinavir
ritonavir
amiodarone
NOT azithromycin
cimetidine
clarithromycin
**diltiazem**
erythromycin
fluvoxamine
grapefruit juice
itraconazole
ketoconazole
mibefradil
nefazodone
troleandomycin
verapamil
INDUCERS
CYP 3A4/3A5/3A7
carbamazepine
phenobarbital
phenytoin
rifabutin
rifampin
St. John's wort
troglitazone
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| Food Interaction |
Diltiazem¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take this medication 30 minutes before meals.Avoid natural licorice.
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| Drug Target |
[Drug Target]
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| Description |
Diltiazem¿¡ ´ëÇÑ Description Á¤º¸ A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [PubChem]
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| Drug Category |
Diltiazem¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihypertensive AgentsCalcium Channel BlockersCalcium-channel blocking agentsCardiovascular AgentsVasodilator Agents
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| Smiles String Canonical |
Diltiazem¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC=C(C=C1)C1SC2=CC=CC=C2N(CCN(C)C)C(=O)C1OC(C)=O
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| Smiles String Isomeric |
Diltiazem¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC=C(C=C1)[C@@H]1SC2=CC=CC=C2N(CCN(C)C)C(=O)[C@@H]1OC(C)=O
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| InChI Identifier |
Diltiazem¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/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
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| Chemical IUPAC Name |
Diltiazem¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ [(2S,3S)-5-(2-dimethylaminoethyl)-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate
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µå·°ÀÎÆ÷ ÀǾàÇмúÁ¤º¸´Â ½ÄǰÀǾàǰ¾ÈÀüóÀÇ Á¦Ç°Çã°¡»çÇ×, Çмú¹®Çå, Á¦¾àȸ»ç Á¦°øÁ¤º¸ µîÀ» ±Ù°Å·Î ÀÛ¼ºµÈ Âü°í Á¤º¸ÀÔ´Ï´Ù.
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ÀüÈ: 02-3486-1061 ¤Ó À̸ÞÀÏ: webmaster@druginfo.co.kr
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The database contains the following fields: The generic name of each chemical For module A10 (liver enzyme composite module): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method) Number of endpoints at which each compound is marginally active (M) Number of endpoints at which each compound is active (A) For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method) Number of ADR reports for each compound, given as <4 or ¡Ã4 Reporting Index value for each compound, except where no shipping units were available (NSU) Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period. DILTIAZEM[GGT Increase][Composite Activity](Score) I(Marginal) 0(Active) 0[Alkaline Phosphatase Increase](Activity Score) I(Number of Rpts) <4(Index value) 0.1[SGOT Increase](Activity Score) I(Number of Rpts) ¡Ã4(Index value) 0.3[SGPT Increase](Activity Score) I(Number of Rpts) <4(Index value) 0.1[LDH Increase](Activity Score) I(Number of Rpts) <4(Index value) 0.1[GGT Increase](Activity Score) I(Number of Rpts) <4(Index value) 0
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