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    | Mechanism of Action | 
    
       Amlodipine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Amlodipine is a calcium channel blocking agent. It inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. 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. Another possible mechanism is that amlodipine inhibits vascular smooth muscle carbonic anhydrase I activity with consecutive pH increase which may be involved in intracelluar calcium influx through calcium channels.
  Valsartan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Valsartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance. 
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    | Pharmacology | 
     
       Amlodipine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Amlodipine, a calcium-channel blocker, is used alone or with benazepril, an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Amlodipine is similar to the peripheral vasodilator nifedipine and other members of the dihydropyridine class.
  Valsartan¿¡ ´ëÇÑ Pharmacology Á¤º¸ Valsartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Unlike the angiotensin receptor antagonist losartan, Valsartan does not have an active metabolite or possess uricosuric effects. 
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    | Metabolism | 
    
       Amlodipine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)
  Valsartan¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2C9 (CYP2C9) 
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    | Absorption | 
    
       Amlodipine¿¡ ´ëÇÑ Absorption Á¤º¸ Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract.
  Valsartan¿¡ ´ëÇÑ Absorption Á¤º¸ Not Available 
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    | Toxicity | 
    
       Amlodipine¿¡ ´ëÇÑ Toxicity Á¤º¸ Gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to an including shock with fatal outcome have been reported.
  Valsartan¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available 
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    | Drug Interactions | 
    
       Amlodipine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Diltiazem	Diltiazem increases the effect and toxicity of amlodipineQuinupristin	This combination presents an increased risk of toxicity
  Valsartan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Almotriptan	Increased risk of CNS adverse effectsEletriptan	Increased risk of CNS adverse effectsFrovatriptan	Increased risk of CNS adverse effectsNaratriptan	Increased risk of CNS adverse effectsRizatriptan	Increased risk of CNS adverse effectsSumatriptan	Increased risk of CNS adverse effectsZolmitriptan	Increased risk of CNS adverse effectsAminophylline	Increases the effect and toxicity of theophyllineDyphylline	Increases the effect and toxicity of theophyllineOxtriphylline	Increases the effect and toxicity of theophyllineTheophylline	Increases the effect and toxicity of theophyllineAmitriptyline	Fluvoxamine increases the effect and toxicity of tricyclicsAmoxapine	Fluvoxamine increases the effect and toxicity of tricyclicsClomipramine	Fluvoxamine increases the effect and toxicity of tricyclicsDesipramine	Fluvoxamine increases the effect and toxicity of tricyclicsDoxepin	Fluvoxamine increases the effect and toxicity of tricyclicsImipramine	Fluvoxamine increases the effect and toxicity of tricyclicsNortriptyline	Fluvoxamine increases the effect and toxicity of tricyclicsProtriptyline	Fluvoxamine increases the effect and toxicity of tricyclicsTrimipramine	Fluvoxamine increases the effect and toxicity of tricyclicsAmphetamine	Risk of serotoninergic syndromeBenzphetamine	Risk of serotoninergic syndromeDextroamphetamine	Risk of serotoninergic syndromeDexfenfluramine	Risk of serotoninergic syndromeDiethylpropion	Risk of serotoninergic syndromeFenfluramine	Risk of serotoninergic syndromeMazindol	Risk of serotoninergic syndromeMethamphetamine	Risk of serotoninergic syndromePhendimetrazine	Risk of serotoninergic syndromePhentermine	Risk of serotoninergic syndromePhenylpropanolamine	Risk of serotoninergic syndromeSibutramine	Risk of serotoninergic syndromeAnisindione	Fluvoxamine increases the effect of the anticoagulantAcenocoumarol	Fluvoxamine increases the effect of the anticoagulantDicumarol	Fluvoxamine increases the effect of the anticoagulantWarfarin	Fluvoxamine increases the effect of the anticoagulantAstemizole	Increased risk of cardiotoxicity and arrhythmiasMesoridazine	Increased risk of cardiotoxicity and arrhythmiasTerfenadine	Increased risk of cardiotoxicity and arrhythmiasThioridazine	Increased risk of cardiotoxicity and arrhythmiasCarbamazepine	Fluvoxamine increases the effect of carbamazepineCilostazol	Fluvoxamine increases the effect of cilostazolClozapine	The antidepressant increases the effect of clozapineDihydroergotamine	Possible ergotism and severe ischemia with this combinationErgotamine	Possible ergotism and severe ischemia with this combinationDuloxetine	Fluvoxamine increases the effect and toxicity of duloxetineEthotoin	Increases the effect of hydantoinFosphenytoin	Increases the effect of hydantoinMephenytoin	Increases the effect of hydantoinPhenytoin	Increases the effect of hydantoinIsocarboxazid	Possible severe adverse reaction with this combinationPhenelzine	Possible severe adverse reaction with this combinationTranylcypromine	Possible severe adverse reaction with this combinationRasagiline	Possible severe adverse reaction with this combinationSelegiline	Possible severe adverse reaction with this combinationLinezolid	Combination associated with possible serotoninergic syndromeLithium	The SSRI increases serum levels of lithiumMethadone	Fluvoxamine increases the effect and toxicity of methadoneMexiletine	Increases the effect and toxicity of mexiletineMirtazapine	Increases the effect adn toxicity of mirtazapineMoclobemide	Increased incidence of adverse effects with this associationOlanzapine	Fluvoxamine increases the effect and toxicity of olanzapineOxycodone	Increased risk of serotonin syndromeTramadol	Increased risk of serotonin syndromeRamelteon	Fluvoxamine increases the levels/toxicity of ramelteonRopinirole	Increases the effect and toxicity of ropiniroleRopivacaine	Increases the effect and toxicity of ropivacaineSt. John's Wort	St. John's Wort increases the effect and toxicity of the SSRITacrine	Fluvoxamine increases the effect of tacrineTizanidine	Fluvoxamine increases the effect/toxicity of tizanidine 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Amlodipine¿¡ ´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 
 
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    | Food Interaction | 
    
       Amlodipine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Grapefruit can significantly increase serum levels of this product.Avoid taking grapefruit or grapefruit juice throughout treatment.Avoid natural licorice.
  Valsartan¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available 
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    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | Description | 
    
       Amlodipine¿¡ ´ëÇÑ Description Á¤º¸ A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [PubChem]
  Valsartan¿¡ ´ëÇÑ Description Á¤º¸ Valsartan (trade name Diovan®) is an angiotensin II receptor antagonist, acting on the AT1 subtype. In the U.S., valsartan is indicated for treatment of high blood pressure, of congestive heart failure (CHF), and post-myocardial infarction (MI). In 2005, Diovan® was prescribed more than 12 million times in the United States. 
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    | Dosage Form | 
    
       Amlodipine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Tablet	Oral
  Valsartan¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	OralTablet	Oral 
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    | Drug Category | 
    
       Amlodipine¿¡ ´ëÇÑ Drug_Category Á¤º¸ AntianginalsAntihypertensive AgentsCalcium Channel BlockersVasodilator Agents
  Valsartan¿¡ ´ëÇÑ Drug_Category Á¤º¸ Angiotensin II Receptor AntagonistsAntihypertensive Agents 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Amlodipine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCOC(=O)C1=C(COCCN)NC(C)=C(C1C1=CC=CC=C1Cl)C(=O)OC
  Valsartan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCCCC(=O)N(CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1)C(C(C)C)C(O)=O 
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    | Smiles String Isomeric | 
    
       Amlodipine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CCOC(=O)C1=C(COCCN)NC(C)=C([C@@H]1C1=CC=CC=C1Cl)C(=O)OC
  Valsartan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CCCCC(=O)N(CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1)[C@@H](C(C)C)C(O)=O 
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    | InChI Identifier | 
    
       Amlodipine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3
  Valsartan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C24H29N5O3/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H,31,32)(H,25,26,27,28)/t22-/m0/s1/f/h27,31H 
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    | Chemical IUPAC Name | 
    
       Amlodipine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ O3-ethyl O5-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
  Valsartan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid 
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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. AMLODIPINE[GGT Increase][Composite Activity](Score)  I(Marginal)  0(Active)  0[Alkaline Phosphatase Increase](Activity Score)  I(Number of Rpts)  ¡Ã4(Index value)  1[SGOT Increase](Activity Score)  I(Number of Rpts)  ¡Ã4(Index value)  1.3[SGPT Increase](Activity Score)  I(Number of Rpts)  ¡Ã4(Index value)  1.2[LDH Increase](Activity Score)  I(Number of Rpts)  ¡Ã4(Index value)  0.7[GGT Increase](Activity Score)  I(Number of Rpts)  ¡Ã4(Index value)  0.8
 
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