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| DUR (ÀǾàǰ»ç¿ëÆò°¡) |
º´¿ë±Ý±â :
[Ketoconazole]
[»óÈ£ÀÛ¿ë/º´¿ë±Ý±â°Ë»ö]
¿¬·É´ë±Ý±â :
°í½ÃµÈ ¿¬·É±Ý±â ³»¿ëÀº ¾ø½À´Ï´Ù.
[¿¬·É´ë±Ý±â»ó¼¼°Ë»ö]
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| ÈÇб¸Á¶ ¹× ¹°¼º |
[IsoniazidÀÇ ÈÇб¸Á¶Á¤º¸]
 [IsoniazidÀÇ ¹°¼ºÁ¤º¸] CAS number/54-85-3 ATC code/J04AC01 PubChem/3767 DrugBank/APRD01055 Formula/C6H7N3O Mol. mass/137.139 g/mol Bioavailability/ ? Metabolism/liver; CYP450: 2C19, 3A4 inhibitor Excretion/urine (primarily), feces Pregnancy cat./
C Legal status/
prescription only (US) Routes/oral, intramuscular, intravenous Protein binding/Very low (0-10%)
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| µ¶¼ºÁ¤º¸ |
Isoniazid¿¡ ´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 |
Isoniazid¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
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| Pharmacology |
Isoniazid¿¡ ´ëÇÑ Pharmacology Á¤º¸ Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.
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| Metabolism |
Isoniazid¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2E1 (CYP2E1)
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| Protein Binding |
Isoniazid¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Very low (0-10%)
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| Half-life |
Isoniazid¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.
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| Absorption |
Isoniazid¿¡ ´ëÇÑ Absorption Á¤º¸ Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.
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| Pharmacokinetics |
IsoniazidÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
- ÃÖ°í Ç÷Áß ³óµµ µµ´Þ ½Ã°£ : 1-2 ½Ã°£
- Èí¼ö: À§Àå°ü¿¡¼ ¸Å¿ì Àß Èí¼öµÇ³ª À½½Ä¿¡ ÀÇÇØ¼ Èí¼ö°¡ °¨¼Ò
- »ýü³»ÀÌ¿ë·ü : 90 %
- ºÐÆ÷: ³úô¼ö¾×À» Æ÷ÇÔÇÑ ½Åü Àü¹Ý¿¡ ºÐÆ÷
- ´Ü¹é°áÇÕ·ü: 10-15 %
- ´ë»ç: À¯ÀüÀûÀÎ acetylation phenytype¿¡ ÀÇÁ¸ÀûÀ¸·Î °£´ë»ç
- ¹è¼³: ¼Ò½Ç¹Ý°¨±â´Â fast acetylators´Â 30-100 ºÐ, slow acetylators¿¡¼´Â 2-5 ½Ã°£
75-95%°¡ ´¢¹è¼³
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| Biotransformation |
Isoniazid¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase.
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| Toxicity |
Isoniazid¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.
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| Drug Interactions |
Isoniazid¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetaminophen Risk of hepatotoxicityAminophylline Increases the effect and toxicity of theophyllineDyphylline Increases the effect and toxicity of theophyllineOxtriphylline Increases the effect and toxicity of theophyllineTheophylline Increases the effect and toxicity of theophyllinePhenytoin Isoniazid increases the effect of phenytoin in 20% of patientsMephenytoin Isoniazid increases the effect of phenytoin in 20% of patientsFosphenytoin Isoniazid increases the effect of phenytoin in 20% of patientsEthotoin Isoniazid increases the effect of phenytoin in 20% of patientsMeperidine Possible episodes of hypotensionKetoconazole Isoniazid decreases the effect of ketoconazoleWarfarin The agent increases the effect of anticoagulantAcenocoumarol The agent increases the effect of anticoagulantDicumarol The agent increases the effect of anticoagulantAnisindione The agent increases the effect of anticoagulantCarbamazepine Carbamazepine effect is increased as is isoniazid toxicityDisulfiram Increased risk of CNS adverse effects
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸] Isoniazid¿¡ ´ëÇÑ P450 table
SUBSTRATES
CYP 2C9
NSAIDs:
diclofenac
ibuprofen
piroxicam
Oral Hypoglycemic Agents:
tolbutamide
glipizide
Angiotensin II Blockers:
NOT candesartan
irbesartan
losartan
NOT valsartan
celecoxib
fluvastatin naproxen
phenytoin
sulfamethoxazole
tamoxifen
tolbutamide
torsemide
warfarin
INHIBITORS
CYP 2C9
amiodarone
fluconazole
**isoniazid**
INDUCERS
CYP 2C9
rifampin
secobarbital
SUBSTRATES
CYP 2E1
acetaminophen
chlorzoxazone
ethanol
INHIBITORS
CYP 2E1
disulfiram
INDUCERS
CYP 2E1
ethanol
**isoniazid**
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| Food Interaction |
Isoniazid¿¡ ´ëÇÑ Food Interaction Á¤º¸ Avoid aged foods (cheese, red wine), pickled foods, cured foods (bacon/ham), chocolate, fava beans, beer, unless approved by your physician.Take on empty stomach: 1 hour before or 2 hours after meals.Avoid alcohol.Take with a full glass of water.Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
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| Drug Target |
[Drug Target]
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| SNP Á¤º¸ |
Name:Isoniazid (DB00951)
Interacting Gene/Enzyme:Cytochrome P450 2E1 (Gene symbol = CYP2E1) Swissprot P05181
SNP(s):CYP2E1 *1A rs6413419 (G Allele, homozygote)
Effect:Hepatotoxicity
Reference(s):Vuilleumier N, Rossier MF, Chiappe A, Degoumois F, Dayer P, Mermillod B, Nicod L, Desmeules J, Hochstrasser D: CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis. Eur J Clin Pharmacol. 2006 Jun;62(6):423-9. Epub 2006 Apr 27. [PubMed]
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| Description |
Isoniazid¿¡ ´ëÇÑ Description Á¤º¸ Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [PubChem]
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| Dosage Form |
Isoniazid¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Powder OralSyrup OralTablet Oral
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| Drug Category |
Isoniazid¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antitubercular AgentsFatty Acid Synthesis Inhibitors
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| Smiles String Canonical |
Isoniazid¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NNC(=O)C1=CC=NC=C1
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| Smiles String Isomeric |
Isoniazid¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ NNC(=O)C1=CC=NC=C1
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| InChI Identifier |
Isoniazid¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10)/f/h9H
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| Chemical IUPAC Name |
Isoniazid¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ pyridine-4-carbohydrazide
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| Drug-Induced Toxicity Related Proteins |
ISONIAZID ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:N-acetyltransferase Drug:isoniazid Toxicity:erythematosus. [¹Ù·Î°¡±â] Replated Protein:N-acetyltransferase 5 Drug:Isoniazid Toxicity:idiosyncratic hepatotoxicity. [¹Ù·Î°¡±â]
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| ÃֽŹ®Çå°ËÅä |
Extensively Drug-Resistant Tuberculosis in the UnitedStates, 1993-2007.
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Extensively drug-resistant tuberculosis(ÀÌÇÏ XDR-TB)ÀÇ ÃâÇöÀº Àü¼¼°èÀûÀ¸·Î °ø°ø º¸°ÇÀÇ °ü½ÉÀ» ºÒ·¯ÀÏÀ¸ÄѿԴÙ. XDR-TB´Â Ä¡·áÁ¦ ¼±Åÿ¡ Á¦ÇÑÀÌ ÀÖÀ¸¸ç ³ôÀº »ç¸Á·ü°úµµ °ü·ÃÀÌ ÀÖ´Ù. ÀÌ¿¬±¸ÀÇ ¸ñÀûÀº ¹Ì±¹¿¡¼ÀÇ XDR-TBÀÇ epidemiology¸¦±â¼úÇϰí drug-susceptible TB, multidrug-resistant TB(MDR-TB)¿Íºñ±³ÇÏ¿´À» ¶§ XDR-TBÀÇ Æ¯¼ºÀ» ±Ô¸íÇÏ´Â µ¥ ÀÖ´Ù.
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1993³âºÎÅÍ 2007³â»çÀÌ¿¡ º¸°íµÈ TB casesÀÇ descriptive analysis·Î¼, XDR-TB´Â ¾à¹° °¨¼ö¼º °Ë»ç¿¡¼ isoniazid, rifamycin,fluoroquinolone °¢°¢¿¡ ´ëÇÑ ÀúÇ×¼º°ú amikacin, kanamycin ¶Ç´Â capreomycinÁß Àû¾îµµ ÇѰ¡Áö¿¡ ÀúÇ×¼ºÀ» ³ªÅ¸³»´Â °æ¿ì·Î Á¤ÀÇÇÏ¿´´Ù. ÁÖ¿ä°á°ú ÁöÇ¥´Â XDR-TB case counts, trends, XDR-TB¿¡ ´ëÇÑ risk factors, overall survivalÀÌ´Ù.
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À§ÀDZⰣ¿¡ ÃÑ 83 casesÀÇ XDR-TB°¡ º¸°íµÇ¾ú´Ù. 1993³â 18 cases(0.07% of 25,107 TB cases)¿¡¼ 2007³â¿¡´Â 2 cases(0.02% of 13,293 TB cases)·Î°¨¼ÒµÇ¾ú´Ù. HIV test °á°ú¸¦ ¾Ë°í ÀÖ´Â »ç¶÷µé Áß 31¸í(53%)ÀÌ HIV-positive¿´´Ù. MDR-TB¿Í ºñ±³ÇÏ¿´À» ¶§ XDR-TBÀÇ °æ¿ì disseminated TBÀÏ °¡´É¼ºÀÌ ´õ ³ô¾ÒÀ¸¸ç(prevalenceratio [PR], 2.06; 95% confidence interval [CI], 1.19-3.58), sputum culture¿¡¼À½ÀüµÉ °¡´É¼ºÀº ´õ ³·¾Ò°í(PR, 0.55; 95% CI, 0.33-0.94), °¨¿° ±â°£Àº ´õ ¿¬ÀåµÇ¾ú´Ù(median time to culture conversion, 183 days vs 93 days for MDR-TB;P < .001). XDR-TB¿¡ °¨¿°µÈ 26 cases(35%)´Â Ä¡·á µµÁß »ç¸ÁÇÏ¿´°íÀ̵é Áß 21¸í(81%)ÀºHIV-positive¿´´Ù. »ç¸Á·üÀºdrug-susceptible TB(PR, 6.10; 95% CI, 3.65-10.20), MDR-TB(PR, 1.82; 95% CI,1.10-3.02)º¸´Ù XDR-TB¿¡¼ ´õ ³ô¾Ò´Ù.
°á·Ð
1993³â ÀÌ·¡·Î ¹Ì±¹¿¡¼ÀÇ XDR-TBÀÇ cases´Â Á¡Â÷ °¨¼ÒµÇ¾î TB¿Í HIV/AIDS °ü¸®ÀÇ Çâ»óÀ» º¸¿©ÁÖ°í ÀÖÁö¸¸, cases´Â °è¼Ó º¸°íµÇ°í ÀÖ´Ù.
JAMA. 2008 Nov 12;300(18):2153-60.
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The database contains the following fields: The generic name of each chemical For module A10 (liver enzyme composite module): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method) Number of endpoints at which each compound is marginally active (M) Number of endpoints at which each compound is active (A) For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method) Number of ADR reports for each compound, given as <4 or ¡Ã4 Reporting Index value for each compound, except where no shipping units were available (NSU) Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period. ISONIAZID[GGT Increase][Composite Activity](Score) A(Marginal) 0(Active) 5[Alkaline Phosphatase Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) 12.7[SGOT Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) 38.7[SGPT Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) 34.7[LDH Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) 10[GGT Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) 8
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