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    | Mechanism of Action | 
    
       Midazolam¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ It is thought that the actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the brain. Benzodiazepines increase the activity of GABA, thereby producing a calming effect, relaxing skeletal muscles, and inducing sleep. Benzodiazepines act as agonists at the benzodiazepine receptors, which form a component of the benzodiazepine-GABA receptor-chloride ionophore complex. Most anxiolytics appear to act through at least one component of this complex to enhance the inhibitory action of GABA. 
     | 
   
  
   
    | Pharmacology | 
     
       Midazolam¿¡ ´ëÇÑ Pharmacology Á¤º¸ Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. Pharmacodynamic properties of midazolam and its metabolites, which are similar to those of other benzodiazepines, include sedative, anxiolytic, amnesic and hypnotic activities. Benzodiazepine pharmacologic effects appear to result from reversible interactions with the (gamma)-amino butyric acid (GABA) benzodiazepine receptor in the CNS, the major inhibitory neurotransmitter in the central nervous system. The action of midazolam is readily reversed by the benzodiazepine receptor antagonist, flumazenil. 
     | 
   
  
   
    | Metabolism | 
    
       Midazolam¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2C9 (CYP2C9)Cytochrome P450 2B6 (CYP2B6)Cytochrome P450 3A5 (CYP3A5)Cytochrome P450 2E1 (CYP2E1)Cytochrome P450 2C8 (CYP2C8)Cytochrome P450 2D6 (CYP2D6) 
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    | Protein Binding | 
    
       Midazolam¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 97% 
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    | Half-life | 
    
       Midazolam¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2.2-6.8 hours 
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    | Absorption | 
    
       Midazolam¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed after oral administration (absolute bioavailability of the midazolam syrup in pediatric patients is about 36%, and intramuscular is greater than 90%). 
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    | Pharmacokinetics | 
    
       MidazolamÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
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 - ºÐÆ÷ : Vd : 0.8-2.5 L/kg.  ¿ïÇ÷¼º½ÉºÎÀü°ú ¸¸¼º ½ÅºÎÀü¿¡¼´Â Áõ°¡ÇÑ´Ù.
 
 - ´Ü¹é°áÇÕ : 95%
 
 - ´ë»ç : °£´ë»ç Å (microsomal¿¡¼)
 
 - »ýü³»ÀÌ¿ë·ü : Æò±Õ 45%
 
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    | Biotransformation | 
    
       Midazolam¿¡ ´ëÇÑ Biotransformation Á¤º¸ Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, (alpha)-hydroxymidazolam, and 4-hydroxymidazolam. 
     | 
   
  
   
    | Toxicity | 
    
       Midazolam¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50=825 mg/kg (Orally in rats). Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs. 
     | 
   
  
   
    | Drug Interactions | 
    
       Midazolam¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amprenavir	Amprenavir increases the effect and toxicity of benzodiazepineFosamprenavir	Amprenavir increases the effect and toxicity of benzodiazepineAprepitant	Aprepitant increases the effect and toxicity of benzodiazepineAtazanavir	Atazanavir increases the effect and toxicity of benzodiazepineCarbamazepine	Carbamazepine reduces the effect of the benzodiazepineCimetidine	Cimetidine increases the effect of benzodiazepineClozapine	Increased risk of toxicityFluconazole	Fluconazole increases the effect of benzodiazepineKava	Kava increases the effect of benzodiazepineOmeprazole	Omeprazole increases the effect of benzodiazepineQuinupristin	This combination presents an increased risk of toxicityRifampin	Rifampin increases the effect of benzodiazepineSt. John's Wort	St. John's Wort could reduce the benzodiazepine effectTelithromycin	Telithromycin increases the effect/toxicity of the benzodiazepineVoriconazole	The imidazole increases the effect of benzodiazepineItraconazole	The imidazole increases the effect of benzodiazepineKetoconazole	The imidazole increases the effect of benzodiazepineClarithromycin	The macrolide increases the effect of benzodiazepineErythromycin	The macrolide increases the effect of benzodiazepineJosamycin	The macrolide increases the effect of benzodiazepineVerapamil	The calcium channel blocker increases the effect and toxicity of benzodiazepineDiltiazem	The calcium channel blocker increases the effect and toxicity of benzodiazepineDelavirdine	The antiviral agent increases the effect and toxicity of benzodiazepineDocetaxel	The agent increases the serum levels and toxicity of docetaxelEfavirenz	The antiviral agent increases the effect and toxicity of benzodiazepineIndinavir	The protease inhibitor increases the effect of benzodiazepineNelfinavir	The protease inhibitor increases the effect of benzodiazepineRitonavir	The protease inhibitor increases the effect of benzodiazepineSaquinavir	The protease inhibitor increases the effect of benzodiazepineEthotoin	Possible increased levels of the hydantoin, decrease of benzodiazepineFosphenytoin	Possible increased levels of the hydantoin, decrease of benzodiazepineMephenytoin	Possible increased levels of the hydantoin, decrease of benzodiazepinePhenytoin	Possible increased levels of the hydantoin, decrease of benzodiazepine 
     | 
   
  
   
    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Midazolam¿¡ ´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 | 
    
       Midazolam¿¡ ´ëÇÑ Food Interaction Á¤º¸ Grapefruit juice slows the product's absorption and significantly increases its bioavailability. 
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    | Drug Target | 
    
      
      [Drug Target]
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    | Description | 
    
       Midazolam¿¡ ´ëÇÑ Description Á¤º¸ A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients.  It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [PubChem] Midazolam is a schedule IV drug in the United States. 
     | 
   
  
   
    | Drug Category | 
    
       Midazolam¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adjuvants, AnesthesiaAnesthetics, IntravenousAnti-anxiety AgentsGABA ModulatorsHypnotics and Sedatives 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Midazolam¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12 
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    | Smiles String Isomeric | 
    
       Midazolam¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12 
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    | InChI Identifier | 
    
       Midazolam¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3 
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    | Chemical IUPAC Name | 
    
       Midazolam¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine 
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                          ÀüÈ: 02-3486-1061 ¤Ó À̸ÞÀÏ: webmaster@druginfo.co.kr
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