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650302080[A10750581]
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\0 ¿ø/1ݼ¿(2006.11.01)(ÇöÀç¾à°¡)
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| Off-label Usage |
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º´¿ë±Ý±â :
°í½ÃµÈ º´¿ë±Ý±â ³»¿ëÀº ¾ø½À´Ï´Ù.
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| µ¶¼ºÁ¤º¸ |
Chlorpheniramine¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â
Dextromethorphan¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â
Ephedrine¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â
Lysozyme¿¡ ´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 |
Caffeine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3¡Ç,5¡Ç-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine act as agonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of caffeine. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon caffeine intake.
Chlorpheniramine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
Dextromethorphan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
Guaifenesin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Guaifenesin may act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing.
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| Pharmacology |
Caffeine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Caffeine, a naturally occurring xanthine derivative like theobromine and the bronchodilator theophylline, is used as a CNS stimulant, mild diuretic, and respiratory stimulant (in neonates with apnea of prematurity). Often combined with analgesics or with ergot alkaloids, caffeine is used to treat migraine and other headache types. Over the counter, caffeine is available to treat drowsiness or mild water-weight gain.
Chlorpheniramine¿¡ ´ëÇÑ Pharmacology Á¤º¸ In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.
Dextromethorphan¿¡ ´ëÇÑ Pharmacology Á¤º¸ Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity.
Guaifenesin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Guaifenesin is an expectorant which increases the output of phlegm (sputum) and bronchial secretions by reducing adhesiveness and surface tension. The increased flow of less viscous secretions promotes ciliary action and changes a dry, unproductive cough to one that is more productive and less frequent. By reducing the viscosity and adhesiveness of secretions, guaifenesin increases the efficacy of the mucociliary mechanism in removing accumulated secretions from the upper and lower airway.
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| Metabolism |
Caffeine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 1A2 (CYP1A2)
Chlorpheniramine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2D6 (CYP2D6)
Dextromethorphan¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2D6 (CYP2D6)
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| Protein Binding |
Caffeine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Low (25 to 36%).
Chlorpheniramine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 72%
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| Half-life |
Caffeine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3 to 7 hours in adults, 65 to 130 hours in neonates
Chlorpheniramine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 21-27 hours
Dextromethorphan¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3-6 hours
Guaifenesin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 1 hour
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| Absorption |
Caffeine¿¡ ´ëÇÑ Absorption Á¤º¸ Readily absorbed after oral or parenteral administration. The peak plasma level for caffeine range from 6-10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours.
Chlorpheniramine¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed in the gastrointestinal tract.
Dextromethorphan¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed from the gastrointestinal tract.
Guaifenesin¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed from the GI tract
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| Pharmacokinetics |
Dextromethorphan HBrÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
- ÁøÇØÀÛ¿ë ¹ßÇö½Ã°£ : 15~30ºÐ À̳»
- ÀÛ¿ëÁö¼Ó½Ã°£ : 6½Ã°£±îÁö
- ´ë»ç : °£´ë»ç
- ¼Ò½Ç : ÁÖ·Î ½Å¹è¼³
Caffeine anhydrousÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
- Èí¼ö : °æ±¸ : ½Å¼ÓÇϰÔ, ¿ÏÀüÈ÷ Èí¼öµÊ (99%)
- ºÐÆ÷ : ¸ðµç ü¾×¿¡ ºÐÆ÷Çϸç, ³úÇ÷°üÀ庮, ŹÝÀ» Åë°úÇϰí, À¯ÁóÀ¸·Îµµ ºÐºñµÊ
- ºÐÆ÷¿ëÀû :
- ½Å»ý¾Æ : 0.92 L/kg
- ¼ºÀÎ : 0.58 L/kg
- ´Ü¹é°áÇÕ : 15-35%
- ´ë»ç : ¼ºÀÎ : °ÅÀÇ ´ëºÎºÐÀÌ °£¿¡¼ ´ë»çµÇ¸ç, Å»¸ÞƿȵǾî paraxanthine (72%), theobromine (20%), theophylline (8%)À¸·Î ´ë»çµÊ
- ¹Ý°¨±â :
- ¹Ì¼÷¾Æ : 65-103 ½Ã°£
- ¿Ï¼÷¾Æ : 82½Ã°£
- 3-4°³¿ù ¿µ¾Æ : 14.4 ½Ã°£
- 5-6°³¿ù ¿µ¾Æ : 2.6 ½Ã°£
- ¼ºÀÎ : 3-7.5 ½Ã°£ (Æò±Õ 4.9 ½Ã°£)
- ÀӽźΠ: 18½Ã°£±îÁö
- Ç÷ÁßÃÖ°í³óµµ µµ´Þ½Ã°£ : 15-45ºÐ
- ¼Ò½Ç :
- ¼ºÀÎ : ¹Ìº¯Èü·Î ½Å¹è¼³µÇ´Â ¾çÀº 0.5-3.5%
- ½Å»ý¾Æ : °ÅÀÇ ´ëºÎºÐ ¹Ìº¯Èü·Î ½Å¹è¼³µÊ
GuaifenesinÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
- Èí¼ö : À§Àå°üÀ¸·ÎºÎÅÍ Àß Èí¼öµÊ.
- ´ë»ç : 60%°¡ °£´ë»çµÊ.
- ¼Ò½Ç : ´ë»çü ¹× ¹Ìº¯Èü·Î ½Å¹è¼³µÊ.
Chlorpheniramine MaleateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
- ´Ü¹é°áÇÕ : 69-72%
- ´ë»ç : °£´ë»ç
- ¹Ý°¨±â : 20-24 ½Ã°£
- ¼Ò½Ç : ´ë»çü, ¾à¹°(3-4%)ÀÌ ½Å¹è¼³µÇ¸ç, 48½Ã°£³»¿¡ ÀüüÀÇ 35%°¡ ¼Ò½ÇµÈ´Ù.
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| Biotransformation |
Caffeine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic cytochrome P450 1A2 (CYP 1A2) is involved in caffeine biotransformation. About 80% of a dose of caffeine is metabolized to paraxanthine (1,7-dimethylxanthine), 10% to theobromine (3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine).
Chlorpheniramine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic via Cytochrome P450 (CYP450) enzymes.
Dextromethorphan¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Rapidly and extensively metabolized to dextrorphan (active metabolite). One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6.
Guaifenesin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Rapidly hydrolyzed (60% within seven hours) and then excreted in the urine, with beta-(2-methoxyphenoxy)-lactic acid as its major urinary metabolite.
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| Toxicity |
Caffeine¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50=127 mg/kg (orally in mice)
Chlorpheniramine¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 306 mg/kg in humans, mild reproductive toxin to women of childbearing age.
Dextromethorphan¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available
Guaifenesin¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 1510 mg/kg (rat, oral)
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| Drug Interactions |
Caffeine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
Chlorpheniramine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Donepezil Possible antagonism of actionGalantamine Possible antagonism of actionRivastigmine Possible antagonism of actionEthotoin The antihistamine increases the effect of hydantoinFosphenytoin The antihistamine increases the effect of hydantoinMephenytoin The antihistamine increases the effect of hydantoinPhenytoin The antihistamine increases the effect of hydantoin
Dextromethorphan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Dihydroquinidine barbiturate Quinidine increases the toxicity of dextromethorphanQuinidine Quinidine increases the toxicity of dextromethorphanQuinidine barbiturate Quinidine increases the toxicity of dextromethorphanFluoxetine Combination associated with possible serotoninergic syndromeIsocarboxazid Possible severe adverse reactionMemantine Increased risk of CNS adverse effectsMoclobemide Increased CNS toxicityParoxetine Combination associated with possible serotoninergic syndromePhenelzine Possible severe adverse reactionRasagiline Possible severe adverse reactionSelegiline Combination associated with possible serotoninergic syndromeSibutramine Combination associated with possible serotoninergic syndromeTerbinafine Terbinafine increases dextromethorphan levelsTranylcypromine Possible severe adverse reaction
Guaifenesin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸] Dextromethorphan¿¡ ´ëÇÑ P450 table Chlorpheniramine¿¡ ´ëÇÑ P450 table
SUBSTRATES
CYP 2D6
Beta Blockers:
S-metoprolol
propafenone
timolol
Antidepressants:
amitriptyline
clomipramine
desipramine
imipramine
paroxetine
Antipsychotics:
haloperidol
risperidone
thioridazine
aripiprazole
codeine
dextromethorphan
duloxetine
flecainide
mexiletine
ondansetron
tamoxifen
tramadol
venlafaxine
INHIBITORS
CYP 2D6
amiodarone
buproprion
**chlorpheniramine**
cimetidine
clomipramine
duloxetine
fluoxetine
haloperidol
methadone
mibefradil
paroxetine
quinidine
ritonavir
INDUCERS
CYP 2D6
N/A
SUBSTRATES
CYP 2D6
Beta Blockers:
S-metoprolol
propafenone
timolol
Antidepressants:
amitriptyline
clomipramine
desipramine
imipramine
paroxetine
Antipsychotics:
haloperidol
risperidone
thioridazine
aripiprazole
codeine
**dextromethorphan**
duloxetine
flecainide
mexiletine
ondansetron
tamoxifen
tramadol
venlafaxine
INHIBITORS
CYP 2D6
amiodarone
buproprion
chlorpheniramine
cimetidine
clomipramine
duloxetine
fluoxetine
haloperidol
methadone
mibefradil
paroxetine
quinidine
ritonavir
INDUCERS
CYP 2D6
N/A
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| Food Interaction |
Chlorpheniramine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with food.Avoid alcohol.
Guaifenesin¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with a full glass of water.Take without regard to meals.
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| Drug Target |
[Drug Target]
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| SNP Á¤º¸ |
Name:Caffeine (DB00201)
Interacting Gene/Enzyme:Cytochrome P450 1A2 (Gene symbol = CYP1A2) Swissprot P05177
SNP(s):rs762551 (C allele)
Effect:Myocardial infarction
Reference(s):Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H: Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006 Mar 8;295(10):1135-41. [PubMed]
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| Description |
Caffeine¿¡ ´ëÇÑ Description Á¤º¸ A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine&
Chlorpheniramine¿¡ ´ëÇÑ Description Á¤º¸ A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine. [PubChem]
Dextromethorphan¿¡ ´ëÇÑ Description Á¤º¸ The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity. [PubChem]
Guaifenesin¿¡ ´ëÇÑ Description Á¤º¸ An expectorant that also has some muscle relaxing action. It is used in many cough preparations. [PubChem]
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| Dosage Form |
Caffeine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule OralElixir OralLiquid OralPill OralSolution OralSolution / drops OralSuppository RectalSuspension OralSyrup OralTablet OralTablet, extended release Oral
Chlorpheniramine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Syrup OralTablet OralTablet, extended release Oral
Dextromethorphan¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule OralLiquid OralLozenge OralStrip OralSuspension OralSyrup OralTablet Oral
Guaifenesin¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Liquid OralSyrup Oral
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| Drug Category |
Caffeine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anorexigenic AgentsCentral Nervous System StimulantsPhosphodiesterase Inhibitors
Chlorpheniramine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Allergic AgentsAntihistaminesAntipruriticsHistamine H1 Antagonists
Dextromethorphan¿¡ ´ëÇÑ Drug_Category Á¤º¸ Analgesics, OpioidAntitussive AgentsExcitatory Amino Acid Antagonists
Guaifenesin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Expectorants
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| Smiles String Canonical |
Caffeine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN1C=NC2=C1C(=O)N(C)C(=O)N2C
Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN(C)CCC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
Dextromethorphan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC2=C(CC3C4CCCCC24CCN3C)C=C1
Guaifenesin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC=CC=C1OCC(O)CO
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| Smiles String Isomeric |
Caffeine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN1C=NC2=C1C(=O)N(C)C(=O)N2C
Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN(C)CC[C@H](C1=CC=C(Cl)C=C1)C1=CC=CC=N1
Dextromethorphan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC2=C(C[C@H]3[C@H]4CCCC[C@@]24CCN3C)C=C1
Guaifenesin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC=CC=C1OC[C@H](O)CO
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| InChI Identifier |
Caffeine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
Chlorpheniramine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C16H19ClN2/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13/h3-9,11,15H,10,12H2,1-2H3
Dextromethorphan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18-/m1/s1
Guaifenesin¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C10H14O4/c1-13-9-4-2-3-5-10(9)14-7-8(12)6-11/h2-5,8,11-12H,6-7H2,1H3
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| Chemical IUPAC Name |
Caffeine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 1,3,7-trimethylpurine-2,6-dione
Chlorpheniramine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine
Dextromethorphan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ Not Available
Guaifenesin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(2-methoxyphenoxy)propane-1,2-diol
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| Drug-Induced Toxicity Related Proteins |
CAFFEINE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Metallothionein Drug:caffeine Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] MALEATE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Intercellular adhesion molecule 1 Drug:maleate Toxicity:hepatic injury. [¹Ù·Î°¡±â]
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