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	      FDA : Cµî±Þ 
				        
				         (cisapride )
				        
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	 °í½ÃµÈ º´¿ë±Ý±â ³»¿ëÀº ¾ø½À´Ï´Ù.
	 
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    | Mechanism of Action | 
    
       Cisapride¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Cisapride acts through the stimulation of the serotonin 5-HT4 receptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. 
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    | Pharmacology | 
     
       Cisapride¿¡ ´ëÇÑ Pharmacology Á¤º¸ Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4 agonist. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity. 
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    | Metabolism | 
    
       Cisapride¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4) 
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    | Protein Binding | 
    
       Cisapride¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 97.5% 
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    | Half-life | 
    
       Cisapride¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 6-12 hours 
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    | Absorption | 
    
       Cisapride¿¡ ´ëÇÑ Absorption Á¤º¸ Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%. 
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    | Pharmacokinetics | 
    
       Cisapride tartrateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
- ÀÛ¿ë¹ßÇö½Ã°£ : 0.5-1 ½Ã°£
 - »ýü³»ÀÌ¿ë·ü : 35-40%
 - ºÐÆ÷ : ºÐÆ÷¿ëÀû : ¾à 180 L
 - ´Ü¹é°áÇÕ : 97.5-98%
 - ´ë»ç : ÁÖ·Î CYP 3A4¿¡ ÀÇÇØ ´ëºÎºÐ norcisapride·Î ´ë»çµÊ
 - ¹Ý°¨±â : 6-12 ½Ã°£
 - Ç÷ÁßÃÖ°í³óµµ µµ´Þ½Ã°£ : 1-1.5 ½Ã°£
 - ¼Ò½Ç : ÁÖ·Î ´ë»çü·Î¼ ´¢ ¹× ´ëº¯À¸·Î ¹è¼³µÊ (¹Ìº¯Èü·Î´Â 10% ¹Ì¸¸)
  
 
	 
	 
	 
	
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    | Biotransformation | 
    
       Cisapride¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Extensively metabolized via cytochrome P450 3A4 enzyme. 
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    | Toxicity | 
    
       Cisapride¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available 
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    | Drug Interactions | 
    
       Cisapride¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetophenazine	Increased risk of cardiotoxicity and arrhythmiasAmiodarone	Increased risk of cardiotoxicity and arrhythmiasAmitriptyline	Increased risk of cardiotoxicity and arrhythmiasAmoxapine	Increased risk of cardiotoxicity and arrhythmiasAmprenavir	Amprenavir increases the effect and toxicity of cisaprideAnisindione	Increases the anticoagulant effectAprepitant	Increased risk of cardiotoxicity and arrhythmiasAstemizole	Increased risk of cardiotoxicity and arrhythmiasAtazanavir	Increased risk of cardiotoxicity and arrhythmiasBepridil	Increased risk of cardiotoxicity and arrhythmiasBretylium	Increased risk of cardiotoxicity and arrhythmiasChlorpromazine	Increased risk of cardiotoxicity and arrhythmiasClarithromycin	Increased risk of cardiotoxicity and arrhythmiasClomipramine	Increased risk of cardiotoxicity and arrhythmiasDelavirdine	Increased risk of cardiotoxicity and arrhythmiasDesipramine	Increased risk of cardiotoxicity and arrhythmiasDicumarol	Increases the anticoagulant effectDihydroquinidine barbiturate	Increased risk of cardiotoxicity and arrhythmiasDiltiazem	Diltiazem increases the levels of cisaprideDisopyramide	Increased risk of cardiotoxicity and arrhythmiasDoxepin	Increased risk of cardiotoxicity and arrhythmiasEfavirenz	Increased risk of cardiotoxicity and arrhythmiasEncainide	Increased risk of cardiotoxicity and arrhythmiasErythromycin	Increased risk of cardiotoxicity and arrhythmiasEthopropazine	Increased risk of cardiotoxicity and arrhythmiasFexofenadine	Increased risk of cardiotoxicity and arrhythmiasFlecainide	Increased risk of cardiotoxicity and arrhythmiasFluconazole	Increased risk of cardiotoxicity and arrhythmiasFluphenazine	Increased risk of cardiotoxicity and arrhythmiasFosamprenavir	Amprenavir increases the effect and toxicity of cisaprideImipramine	Increased risk of cardiotoxicity and arrhythmiasIndinavir	Increased risk of cardiotoxicity and arrhythmiasItraconazole	Increased risk of cardiotoxicity and arrhythmiasJosamycin	Increased risk of cardiotoxicity and arrhythmiasKetoconazole	Increased risk of cardiotoxicity and arrhythmiasMaprotiline	Increased risk of cardiotoxicity and arrhythmiasMesoridazine	Increased risk of cardiotoxicity and arrhythmiasMethdilazine	Increased risk of cardiotoxicity and arrhythmiasNelfinavir	Increased risk of cardiotoxicity and arrhythmiasMibefradil	Mibefradil increases levels of cisaprideNefazodone	Nefazodone increases serum levels of cisaprideAcenocoumarol	Increases the anticoagulant effectNifedipine	Increases the effect and toxicity of nifedipineNortriptyline	Increased risk of cardiotoxicity and arrhythmiasPerphenazine	Increased risk of cardiotoxicity and arrhythmiasPosaconazole	Contraindicated co-administrationProcainamide	Increased risk of cardiotoxicity and arrhythmiasProchlorperazine	Increased risk of cardiotoxicity and arrhythmiasPromazine	Increased risk of cardiotoxicity and arrhythmiasPromethazine	Increased risk of cardiotoxicity and arrhythmiasPropafenone	Increased risk of cardiotoxicity and arrhythmiasPropiomazine	Increased risk of cardiotoxicity and arrhythmiasProtriptyline	Increased risk of cardiotoxicity and arrhythmiasQuinidine	Increased risk of cardiotoxicity and arrhythmiasQuinidine barbiturate	Increased risk of cardiotoxicity and arrhythmiasQuinupristin	This combination presents an increased risk of toxicityRitonavir	Increased risk of cardiotoxicity and arrhythmiasSaquinavir	Increased risk of cardiotoxicity and arrhythmiasSotalol	Increased risk of cardiotoxicity and arrhythmiasTelithromycin	Increased risk of cardiotoxicity and arrhythmiasTerfenadine	Increased risk of cardiotoxicity and arrhythmiasThiethylperazine	Increased risk of cardiotoxicity and arrhythmiasThioridazine	Increased risk of cardiotoxicity and arrhythmiasTrifluoperazine	Increased risk of cardiotoxicity and arrhythmiasTriflupromazine	Increased risk of cardiotoxicity and arrhythmiasTrimeprazine	Increased risk of cardiotoxicity and arrhythmiasTrimipramine	Increased risk of cardiotoxicity and arrhythmiasTroleandomycin	Increased risk of cardiotoxicity and arrhythmiasVoriconazole	Increased risk of cardiotoxicity and arrhythmiasWarfarin	Increases the anticoagulant effectZafirlukast	Increased risk of cardiotoxicity and arrhythmiasZiprasidone	Increased risk of cardiotoxicity and arrhythmiasIbutilide	Increased risk of cardiotoxicity and arrhythmiasMethotrimeprazine	Increased risk of cardiotoxicity and arrhythmias 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Cisapride¿¡ ´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 | 
    
       Cisapride¿¡ ´ëÇÑ Food Interaction Á¤º¸ Increases absorption, take 30 minutes before a meal.Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can significantly increase serum levels of this product. 
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    | Drug Target | 
    
      
      [Drug Target]
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    | Description | 
    
       Cisapride¿¡ ´ëÇÑ Description Á¤º¸ In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias. The FDA issued a warning letter regarding this risk to health care professionals and patients. 
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    | Dosage Form | 
    
       Cisapride¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Suspension	OralTablet	Oral 
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    | Drug Category | 
    
       Cisapride¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Ulcer AgentsGastrointestinal AgentsProkinetic AgentsSerotonin Agonists 
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    | Smiles String Canonical | 
    
       Cisapride¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1CN(CCCOC2=CC=C(F)C=C2)CCC1NC(=O)C1=CC(Cl)=C(N)C=C1OC 
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    | Smiles String Isomeric | 
    
       Cisapride¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CO[C@H]1CN(CCCOC2=CC=C(F)C=C2)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)C=C1OC 
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    | InChI Identifier | 
    
       Cisapride¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C23H29ClFN3O4/c1-30-21-13-19(26)18(24)12-17(21)23(29)27-20-8-10-28(14-22(20)31-2)9-3-11-32-16-6-4-15(25)5-7-16/h4-7,12-13,20,22H,3,8-11,14,26H2,1-2H3,(H,27,29)/f/h27H 
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    | Chemical IUPAC Name | 
    
       Cisapride¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl]-2-methoxybenzamide 
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    | Drug-Induced Toxicity Related Proteins | 
    
      CISAPRIDE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:HERG Drug:cisapride Toxicity:torsade de pointes.  [¹Ù·Î°¡±â] Replated Protein:Misshapen-like kinase(Mink) Drug:cisapride Toxicity:torsade de pointes.  [¹Ù·Î°¡±â] Replated Protein:Potassium voltage-gated channel subfamily KQT member 1 (KvLQT1) Drug:cisapride Toxicity:torsade de pointes.  [¹Ù·Î°¡±â] 
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