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    222  (ÁøÇذŴãÁ¦                                                      )
      
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    Theophylline¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â 
  Ãâó: ±¹¸³µ¶¼º°úÇпø µ¶¼º¹°ÁúÁ¤º¸DB : http://www.nitr.go.kr/nitr/contents/m134200/view.do  | 
   
  
   
    | Mechanism of Action | 
    
       Theophylline¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. 
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    | Pharmacology | 
     
       Theophylline¿¡ ´ëÇÑ Pharmacology Á¤º¸ Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). 
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    | Metabolism | 
    
       Theophylline¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 1A2 (CYP1A2)Adenosine deaminaseCytochrome P450 2E1 (CYP2E1) 
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    | Protein Binding | 
    
       Theophylline¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 40%, primarily to albumin. 
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    | Half-life | 
    
       Theophylline¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 8 hours 
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    | Absorption | 
    
       Theophylline¿¡ ´ëÇÑ Absorption Á¤º¸ Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. 
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    | Pharmacokinetics | 
    
       Theophylline polymeric shelled complexÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
	- Èí¼ö: °æ±¸ 
	
		-  Oxtriphyline(64% theophylline) : Á¦Çü¿¡ µû¶ó 75-100%±îÁö º¯ÇÑ´Ù.
		
 -  Theophylline : Á¦Çü¿¡ µû¶ó 100%±îÁö Èí¼öµÊ
	
  
	
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		-  Vd = 0.45L/kg
		
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	 -  ´ë»ç : °£¿¡¼ demethylation, oxidation
	
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    | Biotransformation | 
    
       Theophylline¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity. 
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    | Toxicity | 
    
       Theophylline¿¡ ´ëÇÑ Toxicity Á¤º¸ Symptoms of overdose include seizures, arrhythmias, and GI effects. 
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    | Drug Interactions | 
    
       Theophylline¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Theophylline¿¡ ´ëÇÑ P450 table
  SUBSTRATES 
CYP 1A2 
clozapine 
cyclobenzaprine 
imipramine 
mexiletine 
naproxen 
riluzole 
tacrine 
**theophylline** 
 INHIBITORS 
CYP 1A2 
cimetidine 
fluoroquinolones 
fluvoxamine 
ticlopidine 
 INDUCERS 
CYP 1A2 
tobacco 
 
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    | Food Interaction | 
    
       Theophylline¿¡ ´ëÇÑ Food Interaction Á¤º¸ Avoid alcohol.Take with food.Avoid excessive quantities of coffee or tea (Caffeine). 
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    | Drug Target | 
    
      
      [Drug Target]
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    | SNP Á¤º¸ | 
    
      Name:Theophylline (DB00277)
 Interacting Gene/Enzyme:Cytochrome P450 1A2 (Gene symbol = CYP1A2) Swissprt P05177
 SNP(s):-2964G>A (A Allele)
 Effect:Poor metabolizer, lower dose requirement
 Reference(s):Obase Y, Shimoda T, Kawano T, Saeki S, Tomari SY, Mitsuta-Izaki K, Matsuse H, Kinoshita M, Kohno S: Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma. Clin Pharmacol Ther. 2003 May;73(5):468-74. [PubMed] 
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    | Description | 
    
       Theophylline¿¡ ´ëÇÑ Description Á¤º¸ A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities.  Theophylline inhibits the 3& 
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    | Drug Category | 
    
       Theophylline¿¡ ´ëÇÑ Drug_Category Á¤º¸ Bronchodilator AgentsPhosphodiesterase InhibitorsRespiratory Smooth Muscle RelaxantsVasodilator Agents 
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    | Smiles String Canonical | 
    
       Theophylline¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN1C(=O)N(C)C2=C(NC=N2)C1=O 
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    | Smiles String Isomeric | 
    
       Theophylline¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN1C(=O)N(C)C2=C(NC=N2)C1=O 
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    | InChI Identifier | 
    
       Theophylline¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9)/f/h8H 
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    | Chemical IUPAC Name | 
    
       Theophylline¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 1,3-dimethyl-7H-purine-2,6-dione 
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    | Drug-Induced Toxicity Related Proteins | 
    
      THEOPHYLLINE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Renin  Drug:theophylline Toxicity:low blood pressure .  [¹Ù·Î°¡±â] Replated Protein:Acid sphingomyelinase-like phosphodiesterase Drug:Theophylline Toxicity:emetic side effect.  [¹Ù·Î°¡±â] Replated Protein:Alanine aminotransferase Drug:theophylline  Toxicity:metabolic acidosis.  [¹Ù·Î°¡±â] 
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