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	      FDA : Cµî±Þ 
				        
				         (ketoconazole; )
				        
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	          »ó±â ÀÓºÎÅõ¿©¿¡ ´ëÇÑ Á¤º¸´Â Àü»êó¸® µÇ¸é¼ ÀÔ·Â ¿À·ù °¡´É¼ºÀÌ Á¸ÀçÇÕ´Ï´Ù. ¿À·ù °¡´É¼ºÀ» ÃÖ¼ÒÈÇϱâ À§ÇÏ¿© ¸¹Àº ³ë·ÂÀ» ±â¿ïÀ̰í ÀÖÀ¸³ª, ±× Á¤È®¼º¿¡ ´ëÇÏ¿© È®½ÅÀ» µå¸± ¼ö ¾ø½À´Ï´Ù. ÀÌ¿¡ ´ëÇØ ȸ»ç´Â Ã¥ÀÓÀ» ÁöÁö ¾Ê½À´Ï´Ù.
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    | º¸°ü»ó ÁÖÀÇ | 
    
      
    	
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    º´¿ë±Ý±â :
     
	 °í½ÃµÈ º´¿ë±Ý±â ³»¿ëÀº ¾ø½À´Ï´Ù.
	 
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    | Mechanism of Action | 
    
       Ketoconazole¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Ketoconazole interacts with 14-¥á demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. 
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    | Pharmacology | 
     
       Ketoconazole¿¡ ´ëÇÑ Pharmacology Á¤º¸ Ketoconazole, like clotrimazole, fluconazole, itraconazole, and miconazole, is an imidazole antifungal agent. 
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    | Metabolism | 
    
       Ketoconazole¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2C9 (CYP2C9)Cytochrome P450 2C19 (CYP2C19)Cytochrome P450 3A5 (CYP3A5)Cytochrome P450 1A2 (CYP1A2)Cytochrome P450 2C8 (CYP2C8)Cytochrome P450 1A1 (CYP1A1)Cytochrome P450 2D6 (CYP2D6) 
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    | Protein Binding | 
    
       Ketoconazole¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 99% (in vitro, plasma protein binding) 
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    | Half-life | 
    
       Ketoconazole¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2 hours 
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    | Absorption | 
    
       Ketoconazole¿¡ ´ëÇÑ Absorption Á¤º¸ Moderate 
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    | Biotransformation | 
    
       Ketoconazole¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic 
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    | Toxicity | 
    
       Ketoconazole¿¡ ´ëÇÑ Toxicity Á¤º¸ Hepatotoxicity, LD50=86 mg/kg (orally in rat) 
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    | Drug Interactions | 
    
       Ketoconazole¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Alfentanil	The imidazole increases the effect and toxicity of alfentanilAlprazolam	The imidazole increases the effect of the benzodiazepineAmitriptyline	The imidazole increases the effect and toxicity of the tricyclicAnisindione	The imidazole increases the effect of the anticoagulantAripiprazole	The imidazole increases the effect of aripiprazoleBosentan	The imidazole increases the effect and toxicity of bosentanBudesonide	The imidazole increases levels/effect of budesonideCarbamazepine	The imidazole increases the effect of carbamazepineChlordiazepoxide	The imidazole increases the effect of the benzodiazepineCilostazol	The imidazole increases the effect of cilostazolCinacalcet	The imidazole increases the effect and toxicity of cinacalcetClonazepam	The imidazole increases the effect of the benzodiazepineClorazepate	The imidazole increases the effect of the benzodiazepineCyclosporine	The imidazole increases the effect of immunosuppressantDiazepam	The imidazole increases the effect of the benzodiazepineDicumarol	The imidazole increases the effect of the anticoagulantAcenocoumarol	The imidazole increases the effect of the anticoagulantWarfarin	The imidazole increases the effect of the anticoagulantEplerenone	The imidazole increases the effect and toxicity of eplerenoneEstazolam	The imidazole increases the effect of the benzodiazepineEverolimus	The imidazole increases everolimus levels/toxicityFentanyl	The imidazole increases levels/toxicity of fentanylFlurazepam	The imidazole increases the effect of the benzodiazepineHalazepam	The imidazole increases the effect of the benzodiazepineHaloperidol	The imidazole increases the effect and toxicity of haloperidolImatinib	The imidazole increases the levels of imatinibImipramine	The imidazole increases the effect and toxicity of the tricyclicMethylprednisolone	The imidazole increases the effect and toxicity of the corticosteroidMidazolam	The imidazole increases the effect of the benzodiazepineNortriptyline	The imidazole increases the effect and toxicity of the tricyclicPrednisolone	The imidazole increases the effect and toxicity of the corticosteroidPrednisone	The imidazole increases the effect and toxicity of the corticosteroidQuazepam	The imidazole increases the effect of the benzodiazepineQuinidine	The imidazole increases the effect and toxicity of quinidineQuinidine barbiturate	The imidazole increases the effect and toxicity of quinidineRamelteon	The imidazole increases the levels/toxicity of ramelteonRitonavir	The imidazole increases the effect and toxicity of ritonavirSaquinavir	The imidazole increases the effect and toxicity of saquinavirSildenafil	The imidazole increases the effect and toxicity of sildenafilSirolimus	The imidazole increases the effect and toxicity of sirolimusTacrolimus	The imidazole increases the effect of immunosuppressantTadalafil	The imidazole increases tadalafil levelsTolterodine	The imidazole increases the effect and toxicity of tolterodineTriazolam	The imidazole increases the effect of the benzodiazepineValdecoxib	The imidazole increases the effect and toxicity of valdecoxibVardenafil	The imidazole increases the effect and toxicity of vardenafilVinblastine	The imidazole increases the effect and toxicity of vinblastineVincristine	The imidazole increases the effect and toxicity of the antineoplasicZiprasidone	Ketoconazole increases the effect and toxicity of ziprasidoneTolbutamide	Ketoconazole increases the effect and toxicity of tolbutamideSibutramine	Ketoconazole increases the levels and toxicity of sibutramineRosiglitazone	Ketoconazole increases the effect of rosiglitazoneQuetiapine	Ketoconazole increases the effect/toxicity of quetiapinePioglitazone	Ketoconazole increases the effect of pioglitazoneGalantamine	Ketoconazole increases the effect and toxicity of galantamineIndinavir	Ketoconazole increases the effect of indinavirIrinotecan	Ketoconazole increases the effect and toxicity of irinotecanTrazodone	This strong CYP3A4 inhibitor increases the effect and toxicity of trazodoneSunitinib	Possible increase in sunitinib levelsSucralfate	Sucralfate decreases the absorption of the imidazoleSolifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolismAlfuzosin	The antifungal increases the effect of alfuzosinAlmotriptan	This potent CYP3A4 inhibitor increases the effect and toxicity of the triptanAprepitant	This CYP3A4 inhibitor increases the effect and toxicity of aprepitantCiclesonide	Increased effects/toxicity of ciclesonideDarifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolismDocetaxel	The agent increases the serum levels and toxicity of docetaxelDofetilide	This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilideEletriptan	This potent CYP3A4 inhibitor increases the effect and toxicity of the triptanErlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinibGefitinib	This CYP3A4 inhibitor increases levels/toxicity of gefitinibIsoniazid	Isoniazid decreases the effect of ketoconazoleNevirapine	Nevirapine decreases the effect of ketoconazoleRifampin	Rifampin dereases the effect of the imidazoleRanolazine	Increased levels of ranolazine - risk of toxicityTerfenadine	Increased risk of cardiotoxicity and arrhythmiasPimozide	Increased risk of cardiotoxicity and arrhythmiasCisapride	Increased risk of cardiotoxicity and arrhythmiasAstemizole	Increased risk of cardiotoxicity and arrhythmiasAtorvastatin	Increased risk of myopathy/rhabdomyolysisCerivastatin	Increased risk of myopathy/rhabdomyolysisLovastatin	Increased risk of myopathy/rhabdomyolysisSimvastatin	Increased risk of myopathy/rhabdomyolysisAluminium	The antacid decreases the effect of the imidazoleBismuth	The antacid decreases the effect of the imidazoleMagnesium	The antacid decreases the effect of the imidazoleMagnesium oxide	The antacid decreases the effect of the imidazoleCalcium	The antacid decreases the effect of the imidazoleBuspirone	The macrolide increases the effect and toxicity of buspironeCimetidine	The anti-H2 decreases the absorption of the imidazoleFamotidine	The anti-H2 decreases the absorption of the imidazoleNizatidine	The anti-H2 decreases the absorption of the imidazoleRanitidine	The anti-H2 decreases the absorption of the imidazoleDihydroergotamine	Possible ergotism and sever ischemia with this combinationErgotamine	Possible ergotism and sever ischemia with this combinationEsomeprazole	The proton pump inhibitor decreases the absorption of imidazoleLansoprazole	The proton pump inhibitor decreases the absorption of imidazoleOmeprazole	The proton pump inhibitor decreases the absorption of imidazolePantoprazole	The proton pump inhibitor decreases the absorption of imidazoleRabeprazole	The proton pump inhibitor decreases the absorption of imidazoleEthinyl Estradiol	This anti-infectious agent could decrease the effect of the oral contraceptiveMestranol	This anti-infectious agent could decrease the effect of the oral contraceptive 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Ketoconazole¿¡ ´ëÇÑ P450 table
  SUBSTRATES 
CYP 2C19 
Proton Pump Inhibitors: 
omeprazole 
lansoprazole 
pantoprazole 
rabeprazole 
Anti-epileptics: 
diazepam 
phenytoin 
phenobarbitone 
amitriptyline 
clomipramine 
clopidogrel 
cyclophosphamide 
progesterone 
 INHIBITORS 
CYP 2C19 
fluoxetine 
fluvoxamine 
**ketoconazole** 
lansoprazole 
omeprazole 
ticlopidine 
 INDUCERS 
CYP 2C19 
N/A 
  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 | 
    
       Ketoconazole¿¡ ´ëÇÑ Food Interaction Á¤º¸ Avoid alcohol.Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.Take with food. 
     | 
   
  
   
    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | Description | 
    
       Ketoconazole¿¡ ´ëÇÑ Description Á¤º¸ Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [PubChem] 
     | 
   
  
   
    | Drug Category | 
    
       Ketoconazole¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antifungal AgentsAntifungals 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Ketoconazole¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(=O)N1CCN(CC1)C1=CC=C(OCC2COC(CN3C=CN=C3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1 
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    | Smiles String Isomeric | 
    
       Ketoconazole¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1 
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    | InChI Identifier | 
    
       Ketoconazole¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3/t23-,26-/m1/s1 
     | 
   
  
   
    | Chemical IUPAC Name | 
    
       Ketoconazole¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 1-[4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone 
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                ÃÖ±ÙÁ¤º¸¼öÁ¤ÀÏ 2020-05-13
              
 
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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. 
                          Á¤º¸ÀÇ Á¤È®¼ºÀ» À§ÇØ ³ë·ÂÇϰí ÀÖÀ¸³ª ÆíÁý»óÀÇ ¿À·ù, Çã°¡»çÇ× º¯°æ, Ãß°¡ÀûÀÎ Çмú¿¬±¸ ¶Ç´Â Àӻ󿬱¸ ¹ßÇ¥ µîÀ¸·Î ÀÎÇØ ¹ß»ýÇÏ´Â ¹®Á¦¿¡ ´ëÇØ µå·°ÀÎÆ÷´Â 
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                            ¹Ýµå½Ã Á¦Á¶¡¤¼öÀÔ»ç, ÆÇ¸Å»ç, ÀÇ»ç, ¾à»ç¿¡°Ô ÃÖÁ¾ÀûÀ¸·Î È®ÀÎÇϽñ⠹ٶø´Ï´Ù.
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