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                    ¿¡ÆÄ¼Ö°Ö  EFASOL GEL[Erythromycin , Tretinoin]  
                    
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    | Related FDA Approved Drug | 
    
       
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	          ÀüüÀӽŠ±â°£º°·Î ¿©·¯µî±ÞÀÌ Á¸ÀçÇÒ ¼ö ÀÖÀ¸¸ç °¡Àå À§Çèµµ°¡ ³ôÀº Á¤º¸¸¸ º¸¿©Áý´Ï´Ù. ´Ü, º¹ÇÕÁ¦ÀÇ °æ¿ì ¸ðµç º¹ÇÕÁ¦¼ººÐ¿¡ ´ëÇÑ ÀÓºÎÅõ¿©µî±ÞÀÌ Ç¥½ÃµÈ°ÍÀº Àý´ë ¾Æ´Ï¸ç Ç¥½ÃµÈ°ÍÁß¿¡ °¡Àå À§Çèµµ°¡ ³ôÀº Á¤º¸¸¸ ³ªÅ¸³³´Ï´Ù. 
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    | Mechanism of Action | 
    
       Erythromycin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Erythromycin acts by penetrating the bacterial cell membrane and reversibly binding to the 50 S subunit of bacterial ribosomes or near the ¡°P¡± or donor site so that binding of tRNA (transfer RNA) to the donor site is blocked. Translocation of peptides from the ¡°A¡± or acceptor site to the ¡°P¡± or donor site is prevented, and subsequent protein synthesis is inhibited. Erythromycin is effective only against actively dividing organisms. The exact mechanism by which erythmromycin reduces lesions of acne vulgaris is not fully known: however, the effect appears to be due in part to the antibacterial activity of the drug.
  Tretinoin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Tretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. Tretinoin promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When Tretinoin is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown. 
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    | Pharmacology | 
     
       Erythromycin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Erythromycin is produced by a strain of Streptomyces erythraeus and belongs to the macrolide group of antibiotics. After absorption, erythromycin diffuses readily into most body fluids. In the absence of meningeal inflammation, low concentrations are normally achieved in the spinal fluid, but the passage of the drug across the blood-brain barrier increases in meningitis. Erythromycin is excreted in breast milk. The drug crosses the placental barrier, but fetal plasma levels are low. Erythromycin is not removed by peritoneal dialysis or hemodialysis.
  Tretinoin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL). 
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    | Protein Binding | 
    
       Erythromycin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Erythromycin is largely bound to plasma proteins, and the freely dissociating bound fraction after administration of erythromycin base represents 90% of the total erythromycin absorbed.
  Tretinoin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ > 95% 
     | 
   
  
   
    | Half-life | 
    
       Erythromycin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 1.5 hours
  Tretinoin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 0.5-2 hours 
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    | Absorption | 
    
       Erythromycin¿¡ ´ëÇÑ Absorption Á¤º¸ Orally administered erythromycin base and its salts are readily absorbed in the microbiologically active form. Topical application of the ophthalmic ointment to the eye may result in absorption into the cornea and aqueous humor.
  Tretinoin¿¡ ´ëÇÑ Absorption Á¤º¸ 1-31% (topical) 
     | 
   
  
   
    | Pharmacokinetics | 
    
       TretinoinÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
- ÀÛ¿ë¹ßÇö½Ã°£ : ¿©µå¸§ : ±¹¼ÒÀû¿ë : 2-3ÁÖ
 - ÃÖ´ëÈ¿°ú ¹ßÇö½Ã°£ : ¿©µå¸§ : ±¹¼ÒÀû¿ë : 6ÁÖ ÀÌ»ó
 - Èí¼ö : ±¹¼Ò Àû¿ë : Àü½Å Èí¼ö´Â Àû´Ù.
 - ´ë»ç : Àü½ÅÀûÀ¸·Î Èí¼öµÈ ¼Ò·®Àº °£¿¡¼ ´ë»çµÈ´Ù.
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	 ErythromycinÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
-  Èí¼ö : 
   -  ´Ù¾çÇÏÁö¸¸ base Çüź¸´Ù ¿°ÀÇ ÇüŰ¡ ´õ Àß Èí¼öµÈ´Ù.
 
    -  ÀϹÝÀûÀ¸·Î À½½Ä¹° Á¸Àç½Ã Èí¼ö°¡ Áö¿¬µÇ³ª ethylsuccinate¿°Àº ½ÄÁ÷ÈÄ¿¡ º¹¿ëÇϸé Èí¼ö°¡ Áõ°¡µÈ´Ù.
 
    -  Èí¼ö·üÀÇ Â÷ÀÌ·Î erythromycin ethylsuccinate 200 mg´Â erythromycin base 125 m¿Í µ¿µîÇÑ Ç÷Á߳󵵸¦ ³ªÅ¸³½´Ù.
   
 -  »ýü³»ÀÌ¿ë·ü : °æ±¸ :  18-45%
 
 -  ºÐÆ÷ : 
-  ŹÝÅë°ú, À¯ÁóºÐºñ
 
 -  ³úô¼ö¾×À¸·ÎÀÇ ºÐÆ÷´Â ¿°ÁõÀÌ ÀÖ´Â °æ¿ì¿¡µµ ¹Ì¹ÌÇÏ´Ù.
 
 -  ³úô¼ö¾× ´ë Ç÷¾×ÀÇ ³óµµ ºñ (%) : 
	-  Á¤»ó ³ú¸· : 1-12
 
	 -  °¨¿°µÈ ³ú¸· : 7-25
     
 -  ´Ü¹é°áÇÕ : 75-90%
 
 -  ´ë»ç : °£¿¡¼ demethylation
 
 -  ¹Ý°¨±â : 1.5-2 ½Ã°£
	-  ¸»±â ½ÅºÎÀüȯÀÚ : 5-6 ½Ã°£
  
 -  Ç÷ÁßÃÖ°í³óµµ µµ´Þ½Ã°£ : 
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 -  Ethylsuccinate ¿° : 0.5-2.5 ½Ã°£
  
 -  ¼Ò½Ç : ´ëºÎºÐ ´ãÁó¹è¼³µÇ°í, 2-15%°¡ ¹Ìº¯Èü·Î ½Å¹è¼³
   
     | 
   
  
   
    | Biotransformation | 
    
       Erythromycin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Extensively metabolized - after oral administration, less than 5% of the administered dose can be recovered in the active form in the urine.
  Tretinoin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic 
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    | Toxicity | 
    
       Erythromycin¿¡ ´ëÇÑ Toxicity Á¤º¸ Symptoms of overdose include diarrhea, nausea, stomach cramps, and vomiting.
  Tretinoin¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available 
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    | Drug Interactions | 
    
       Erythromycin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Alfentanil	The macrolide increases the effect and toxicity of alfentanilAlprazolam	The macrolide increases the effect of the benzodiazepineAminophylline	The macrolide increases the effect and toxicity of theophyllineAmiodarone	Increased risk of cardiotoxicity and arrhythmiasAnisindione	The macrolide increases anticoagulant effectAprepitant	This CYP3A4 inhibitor increases effect and toxicity of aprepitantAstemizole	Increased risk of cardiotoxicity and arrhythmiasAtorvastatin	The macrolide possibly increases the statin toxicityBretylium	Increased risk of cardiotoxicity and arryhthmiasBromocriptine	Erythromycin increases serum levels of bromocriptineBuspirone	The macrolide increases the effect and toxicity of buspironeCabergoline	Erythromycin increases serum levels and toxicity of cabergolineCarbamazepine	The macrolide increases the effect of carbamazepineCerivastatin	The macrolide possibly increases the statin toxicityCilostazol	Erythromycin increases the effect of cilostazolCinacalcet	This macrolide increases the serum levels and toxicity of cinacalcetCisapride	Increased risk of cardiotoxicity and arrhythmiasCitalopram	Possible serotoninergic syndrome with this combinationClozapine	Erythromycin increases the effect of clozapineColchicine	Severe colchicine toxicity can occurCyclosporine	The macrolide increases the effect of cyclosporineDiazepam	The macrolide increases the effect of the benzodiazepineDicumarol	The macrolide increases anticoagulant effectDigoxin	The macrolide increases the effect of digoxin in 10% of patientsDihydroergotamine	Possible ergotism and severe ischemia with this combinationDihydroergotoxine	Possible ergotism and severe ischemia with this combinationDyphylline	The macrolide increases the effect and toxicity of theophyllineDisopyramide	Increased risk of cardiotoxicity and arrhythmiasDivalproex sodium	Erythromycin increases the effect of valproic acidDocetaxel	The agent increases the serum levels and toxicity of docetaxelDofetilide	Increased risk of cardiotoxicity and arrhythmiasEletriptan	The macrolide increases the effect and toxicity of eletriptanEplerenone	This CYP3A4 inhibitor increases the effect and toxicity of eplerenoneErgotamine	Possible ergotism and severe ischemia with this combinationErlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinibImatinib	The macrolide increases levels of imatinibFelodipine	Erythromycin increases the effect of felodipineFluoxetine	Possible serotoninergic syndrome with this combinationGefitinib	This CYP3A4 inhibitor increases levels/toxicity of gefitinibGrepafloxacin	Increased risk of cardiotoxicity and arrhythmiasItraconazole	The macrolide increases the effect and toxicity of itraconazoleLevofloxacin	Increased risk of cardiotoxicity and arrhythmiasMesoridazine	Increased risk of cardiotoxicity and arrhythmiasMethylergonovine	Possible ergotism and severe ischemia with this combinationLovastatin	The macrolide possibly increases the statin toxicityMethylprednisolone	The macrolide increases the effect of corticosteroidMethysergide	Possible ergotism and severe ischemia with this combinationMidazolam	The macrolide increases the efect of the benzodiazepineMoxifloxacin	Increased risk of cardiotoxicity and arrhythmiasOxtriphylline	The macrolide increases the effect and toxicity of theophyllinePimozide	Increased risk of cardiotoxicity and arrhythmiasQuetiapine	This macrolide increases the effect/toxicity of quetiapineQuinidine	Increased risk of cardiotoxicity and arrhythmiasQuinidine barbiturate	Increased risk of cardiotoxicity and arrhythmiasQuinupristin	This combination presents an increased risk of toxicityRanolazine	Increased levels of ranolazine - risk of toxicityRepaglinide	This macrolide increases effect of repaglinideRifabutin	The rifamycin decreases the effect of the macrolideRifampin	The rifamycin decreases the effect of the macrolideRitonavir	Increased toxicity of both agentsSertraline	Possible serotoninergic syndrome with this combinationSibutramine	Erythromycin increases the effect and toxicity of sibutramineSildenafil	The macrolide increases the effect and toxicity of sildenafilSimvastatin	The macrolide possibly increases the statin toxicitySirolimus	The macrolide increases sirolimus levelsSotalol	Increased risk of cardiotoxicity and arrhythmiasSparfloxacin	Increased risk of cardiotoxicity and arrhythmiasTacrolimus	Erythromycin increases the effect and toxicity of tacrolimusTerfenadine	Increased risk of cardiotoxicity and arrhythmiasTheophylline	The macrolide increases the effect and toxicity of theophyllineThioridazine	Increased risk of cardiotoxicity and arrhythmiasVerapamil	Increased risk of cardiotoxicity and arrhythmiasTriazolam	The macrolide increases the effect of the benzodiazepineVardenafil	The macrolide increases the effect and toxicity of vardenafilVinblastine	Erythromycin increases vinblastine toxicityWarfarin	The macrolide increases anticoagulant effectZafirlukast	Erythromycin decreases the effect of zafirlukastErgonovine	Possible ergotism and severe ischemia with this combinationEverolimus	The macrolide increases everolimus levels/toxicityLincomycin	Possible antagonism of action with this combinationAcenocoumarol	The macrolide increases anticoagulant effect
  Tretinoin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Erythromycin¿¡ ´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 
  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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    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | Description | 
    
       Erythromycin¿¡ ´ëÇÑ Description Á¤º¸ Erythromycin is a bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [PubChem]
  Tretinoin¿¡ ´ëÇÑ Description Á¤º¸ Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL). 
     | 
   
  
   
    | Dosage Form | 
    
       Erythromycin¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule, coated	OralLiquid	DentalLiquid	OralOintment	OphthalmicPowder	IntravenousPowder	OralPowder, for solution	IntravenousPowder, for solution	OralPowder, for suspension	OralSuspension	OralTablet	Oral
  Tretinoin¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	OralCream	TopicalGel	TopicalLiquid	Topical 
     | 
   
  
   
    | Drug Category | 
    
       Erythromycin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Bacterial Agents
  Tretinoin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antineoplastic AgentsCell Stimulants and ProliferantsKeratolytic Agents 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Erythromycin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCC1OC(=O)C(C)C(OC2CC(C)(OC)C(O)C(C)O2)C(C)C(OC2OC(C)CC(C2O)N(C)C)C(C)(O)CC(C)C(=O)C(C)C(O)C1(C)O
  Tretinoin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(O)=O 
     | 
   
  
   
    | Smiles String Isomeric | 
    
       Erythromycin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O
  Tretinoin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(C)=C/C(O)=O 
     | 
   
  
   
    | InChI Identifier | 
    
       Erythromycin¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C37H67NO13/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-/m1/s1
  Tretinoin¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/f/h21H 
     | 
   
  
   
    | Chemical IUPAC Name | 
    
       Erythromycin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-dimethylamino-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione
  Tretinoin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid 
     | 
   
  
   
    | Drug-Induced Toxicity Related Proteins | 
    
      ERYTHROMYCIN ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Misshapen-like kinase(Mink) Drug:Erythromycin Toxicity:torsade de pointes.  [¹Ù·Î°¡±â] Replated Protein:Potassium voltage-gated channel subfamily KQT member 1 (KvLQT1) Drug:Erythromycin Toxicity:torsade de pointes.  [¹Ù·Î°¡±â] Replated Protein:Intercellular adhesion molecule 1  Drug:erythromycin Toxicity:pathogenesis of infusion phlebitis.  [¹Ù·Î°¡±â] Replated Protein:HERG Drug:Erythromycin Toxicity:torsade de pointes.  [¹Ù·Î°¡±â] Replated Protein:Alanine aminotransferase Drug:erythromycin  Toxicity:adverse gastrointestinal effects.  [¹Ù·Î°¡±â] 
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