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                    ÄÚ¸®¸¶À̽ſ¡ÇÁ±Í¾à  COLIMYCIN-F EAR.[Colistin Sulfate , Hydrocortisone acetate , Neomycin Sulfate]  
                    
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        640004740[A01001841]  
	    
	    
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    | Mechanism of Action | 
    
       Colistin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Colistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.
  Hydrocortisone¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.
  Neomycin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Aminoglycosides like neomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically neomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. 
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    | Pharmacology | 
     
       Colistin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Colistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.
  Hydrocortisone¿¡ ´ëÇÑ Pharmacology Á¤º¸ Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.
  Neomycin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Neomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses. 
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    | Metabolism | 
    
       Colistin¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Not Available
  Hydrocortisone¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)
  Neomycin¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Not Available 
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    | Protein Binding | 
    
       Colistin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Not Available
  Hydrocortisone¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 95%
  Neomycin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Protein binding studies have shown that the degree of aminoglycoside protein binding is low and, depending upon the methods used for testing, may be between 0% and 30%. 
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    | Half-life | 
    
       Colistin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 5 hours
  Hydrocortisone¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 6-8 hours
  Neomycin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2 to 3 hours 
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    | Absorption | 
    
       Colistin¿¡ ´ëÇÑ Absorption Á¤º¸ Very poor absorption from gastrointestinal tract.
  Hydrocortisone¿¡ ´ëÇÑ Absorption Á¤º¸ Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.
  Neomycin¿¡ ´ëÇÑ Absorption Á¤º¸ Poorly absorbed from the normal gastrointestinal tract. Although only approximately 3% of neomycin is absorbed through intact intestinal mucosa, significant amounts may be absorbed through ulcerated or denuded mucosa or if inflammation is present. 
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    | Pharmacokinetics | 
    
       Colistin SulfateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
-  Èí¼ö : °æ±¸ : 
	
	-  ¼ºÀÎ : ¼Ò·®ÀÌ À§Àå°ü¿¡¼ Èí¼ö
	
 -  ¿µ¾Æ : ¿¹ÃøÀÌ ºÒ°¡´ÉÇϸç, Ç÷Áß³óµµ°¡ ÇöÀúÈ÷ »ó½ÂÇÒ ¼öµµ ÀÖ´Ù.
	
  
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	-  2.8-4.8 ½Ã°£, ½ÅºÎÀü½Ã Áõ°¡
	
 -  ¹«´¢Áõ : 48-72 ½Ã°£
	
  
 -  ¼Ò½Ç : 65-75%°¡ ¹Ìº¯Èü·Î ½Å¹è¼³
  
 Hydrocortisone acetateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
	- Èí¼ö : Á÷ÀåÀ» Á¦¿ÜÇÑ ¸ðµç Åõ¿©°æ·Î¿¡¼ ºü¸£°Ô Èí¼öµÈ´Ù.
	
 - ´ë»ç : °£¿¡¼ ´ë»çµÈ´Ù.
	
 - »ý¸®Àû ¹Ý°¨±â : 8¡12½Ã°£
	
 - ¼Ò½Ç : ÁÖ·Î 17-hydroxysteroids¿Í  17-ketosteroidsÀÇ ÇüÅ·Π½Å¹è¼³µÈ´Ù.
		
 -  ¿ëÇØ¼ºÀÌ Å« ´Ù¸¥ ¾à¹°°ú ºñ±³ÇßÀ» ¶§ hydrocortisone acetate´Â ÀÛ¿ë¹ßÇö½Ã°£Àº ´À¸®Áö¸¸ ÀÛ¿ëÁö¼Ó½Ã°£ÀÌ ±æ´Ù.
 
		 -  Hydrocortisone sodium succinate´Â ¹°¿¡ ½±°Ô ³ì¾Æ »¡¸® Ȱ¼ºÈµÈ´Ù.
  	 
 Neomycin SulfateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
- Èí¼ö : °æ±¸, °æÇÇ : Èí¼öµÇ´Â ¾çÀÌ ¹Ì¹ÌÇÏ´Ù.  (3%)
 - ºÐÆ÷ : ºÐÆ÷¿ëÀû : 0.36 L/kg
 - ´ë»ç : ¼Ò·®ÀÌ °£¿¡¼ ´ë»çµÈ´Ù.
 - ¹Ý°¨±â : 3 ½Ã°£ (³ªÀÌ¿Í ½Å±â´É¿¡ ÀÇÁ¸)
 - Ç÷ÁßÃÖ°í³óµµ µµ´Þ½Ã°£ : 
	
	- °æ±¸ : 1-4 ½Ã°£
	
 - ±ÙÀ°ÁÖ»ç : 2 ½Ã°£ À̳»
	
  
 - ¼Ò½Ç : 
	
	- ÁÖ»çÁ¦ : ½Å¹è¼³ (30-50%°¡ ¹Ìº¯Èü·Î ¹è¼³)
	
 - °æ±¸ : 97%°¡ ¹Ìº¯Èü·Î º¯¹è¼³
	
  
  
     | 
   
  
   
    | Biotransformation | 
    
       Colistin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Not Available
  Hydrocortisone¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic via CYP3A4
  Neomycin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Neomycin undergoes negligible biotransformation after parenteral administration. 
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    | Toxicity | 
    
       Colistin¿¡ ´ëÇÑ Toxicity Á¤º¸ Oral LD50 in rats is 5450 mg/kg. Overdosage with colistimethate can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death.
  Hydrocortisone¿¡ ´ëÇÑ Toxicity Á¤º¸ Side effects include inhibition of bone formation, suppression of calcium absorption and delayed wound healing
  Neomycin¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 200 mg/kg (rat). Because of low absorption, it is unlikely that acute overdosage would occur with oral neomycin. However, prolonged administration could result in sufficient systemic drug levels to produce neurotoxicity, ototoxicity and/or nephrotoxicity. 
     | 
   
  
   
    | Drug Interactions | 
    
       Colistin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
  Hydrocortisone¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Ambenonium	The corticosteroid decreases the effect of anticholinesterasesEdrophonium	The corticosteroid decreases the effect of anticholinesterasesNeostigmine	The corticosteroid decreases the effect of anticholinesterasesPyridostigmine	The corticosteroid decreases the effect of anticholinesterasesAspirin	The corticosteroid decreases the effect of salicylatesBismuth Subsalicylate	The corticosteroid decreases the effect of salicylatesSalicylate-magnesium	The corticosteroid decreases the effect of salicylatesSalicylate-sodium	The corticosteroid decreases the effect of salicylatesSalsalate	The corticosteroid decreases the effect of salicylatesTrisalicylate-choline	The corticosteroid decreases the effect of salicylatesWarfarin	The corticosteroid alters the anticoagulant effectAcenocoumarol	The corticosteroid alters the anticoagulant effectDicumarol	The corticosteroid alters the anticoagulant effectAnisindione	The corticosteroid alters the anticoagulant effectCholestyramine	Cholestyramine decreases the effect of hydrocortisoneColestipol	Cholestyramine decreases the effect of hydrocortisoneAmobarbital	The barbiturate decreases the effect of the corticosteroidAprobarbital	The barbiturate decreases the effect of the corticosteroidButabarbital	The barbiturate decreases the effect of the corticosteroidButalbital	The barbiturate decreases the effect of the corticosteroidButethal	The barbiturate decreases the effect of the corticosteroidDihydroquinidine barbiturate	The barbiturate decreases the effect of the corticosteroidHeptabarbital	The barbiturate decreases the effect of the corticosteroidHexobarbital	The barbiturate decreases the effect of the corticosteroidMethohexital	The barbiturate decreases the effect of the corticosteroidMethylphenobarbital	The barbiturate decreases the effect of the corticosteroidPentobarbital	The barbiturate decreases the effect of the corticosteroidPhenobarbital	The barbiturate decreases the effect of the corticosteroidPrimidone	The barbiturate decreases the effect of the corticosteroidQuinidine barbiturate	The barbiturate decreases the effect of the corticosteroidSecobarbital	The barbiturate decreases the effect of the corticosteroidTalbutal	The barbiturate decreases the effect of the corticosteroidRifampin	The enzyme inducer decreases the effect of the corticosteroidPhenytoin	The enzyme inducer decreases the effect of the corticosteroidMephenytoin	The enzyme inducer decreases the effect of the corticosteroidFosphenytoin	The enzyme inducer decreases the effect of the corticosteroidEthotoin	The enzyme inducer decreases the effect of the corticosteroidMidodrine	Increased arterial pressure
  Neomycin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] 
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    | Food Interaction | 
    
       Hydrocortisone¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with food to reduce irritation. Calcium, phosphorous, potassium, Vitamin A, C, D and zinc needs increased with long term use.
  Neomycin¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available 
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    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | Description | 
    
       Colistin¿¡ ´ëÇÑ Description Á¤º¸ Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally. [PubChem]
  Hydrocortisone¿¡ ´ëÇÑ Description Á¤º¸ The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [PubChem]
  Neomycin¿¡ ´ëÇÑ Description Á¤º¸ A component of neomycin that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed) 
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    | Dosage Form | 
    
       Colistin¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Powder, for solution	Intravenous
  Hydrocortisone¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Aerosol	RectalCream	TopicalEnema	RectalLiquid	TopicalLotion	TopicalOintment	OphthalmicOintment	TopicalPowder, for solution	IntramuscularPowder, for solution	IntravenousTablet	Oral
  Neomycin¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Dressing	TopicalOintment	OphthalmicSolution / drops	Ophthalmic 
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    | Drug Category | 
    
       Colistin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Bacterial Agents
  Hydrocortisone¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-inflammatory Agents
  Neomycin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Bacterial AgentsAntibiotics 
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    | Smiles String Canonical | 
    
       Colistin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCC(C)CCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O)C(C)O
  Hydrocortisone¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC12CCC(=O)C=C1CCC1C3CCC(O)(C(=O)CO)C3(C)CC(O)C21
  Neomycin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NCC1OC(OC2C(N)CC(N)C(O)C2OC2OC(CO)C(OC3OC(CN)C(O)C(O)C3N)C2O)C(N)C(O)C1O 
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    | Smiles String Isomeric | 
    
       Colistin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC[C@@H](C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O)[C@@H](C)O
  Hydrocortisone¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3CC[C@](O)(C(=O)CO)[C@@]3(C)C[C@H](O)[C@H]21
  Neomycin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O)[C@H]2O[C@@H]2O[C@H](CO)[C@@H](O[C@H]3O[C@@H](CN)[C@@H](O)[C@H](O)[C@H]3N)[C@H]2O)[C@H](N)[C@@H](O)[C@@H]1O 
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    | InChI Identifier | 
    
       Colistin¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C52H98N16O13/c1-9-29(6)11-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-27(2)3)66-50(79)39(26-28(4)5)65-45(74)34(15-21-55)60-46(37)75/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76)/t29?,30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+/m1/s1/f/h58-68H
  Hydrocortisone¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1
  Neomycin¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C23H46N6O13/c24-2-7-13(32)15(34)10(28)21(37-7)40-18-6(27)1-5(26)12(31)20(18)42-23-17(36)19(9(4-30)39-23)41-22-11(29)16(35)14(33)8(3-25)38-22/h5-23,30-36H,1-4,24-29H2/t5-,6+,7-,8+,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1 
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    | Chemical IUPAC Name | 
    
       Colistin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-(1-hydroxyethyl)-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-5-methylheptanamide
  Hydrocortisone¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
  Neomycin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2-[(2S,3R,4S,5R)-4-[(2R,3R,4R,5S,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol 
     | 
   
  
   
    | Drug-Induced Toxicity Related Proteins | 
    
      HYDROCORTISONE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Interleukin-8  Drug:hydrocortisone Toxicity:inflammation.  [¹Ù·Î°¡±â] NEOMYCIN ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:NMDA receptor-regulated protein Drug:neomycin Toxicity:excitotoxic activation.  [¹Ù·Î°¡±â] 
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