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14) ¼±ÃµÀûÀ¸·Î thiopurine methyltransferase(TPMT)°¡ °áÇÌµÈ »ç¶÷Àº ÀÌ ¾àÀÇ °ñ¼ö ¾ïÁ¦ È¿°ú¿¡ ºñÁ¤»óÀûÀ¸·Î ¹Î°¨ÇÒ ¼ö ÀÖÀ¸¸ç ÀÌ ¾àÀÇ Åõ¿© Ãʱ⿡ ±Þ¼ÓÇÑ °ñ¼ö ¾ïÁ¦¸¦ Áõ°¡½ÃŰ´Â °æÇâÀÌ ÀÖ´Ù. ÀÌ´Â ¿Ã»ì¶óÁø, ¸Þ»ì¶óÁø, ¶Ç´Â ¼³ÆÄ»ì¶óÁø°ú °°ÀÌ TPMP¸¦ ¾ïÁ¦ÇÏ´Â ¾à¹°°ú º´¿ëÅõ¿©½Ã ´õ¿í Áõ°¡µÉ ¼ö ÀÖ´Ù.
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16) °£Áß½ÉÁ¤¸ÆÆó¼âÁõ, °áÀý¼ºÀç»ý¼º°úÇü¼º µîÀÌ ³ªÅ¸³´Ù´Â º¸°í°¡ ÀÖ´Ù.
17) ÀÌ ¾àÀº hypoxanthine-guanine-phosphoribosyltranseferase°¡ °áÇÌ(Lesch-Nyhan syndrom)µÈ ȯÀÚ¿¡°Ô Åõ¿©½Ã À̵æÀÌ ¾ø´Ù´Â Á¦ÇÑµÈ »ç·Ê°¡ ÀÖÀ¸¹Ç·Î ÀÌ ¾àÀÇ Åõ¿©´Â ¹Ù¶÷Á÷ÇÏÁö ¾Ê´Ù.
18) ½ÅÀå À̽ÄÈÄ ÀÌ ¾àÀ» Åõ¿©¹Þ´Â ³²³àȯÀÚ ¸ðµÎ¿¡°Ô ºÒÀÓÀÌ Áõ°¡µÉ ¼ö ÀÖ´Ù.
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1) Å©»êƾ »êÈÈ¿¼Ò(xanthine oxidase, XO)ÀÇ ¾ïÁ¦´Â ¾ÆÀÚÆ¼¿ÀÇÁ¸° ¶Ç´Â ±× ´ë»ç »ê¹°ÀÎ 6-¸Þ¸£Ä°ÅäǪ¸°ÀÇ Ç÷Àå ³óµµ¸¦ Áõ°¡½ÃÄÑ µ¶¼ºÀ» À¯¹ßÇÒ ¼ö ÀÖ´Ù. ¾Ë·ÎǪ¸®³î, ¿Á½ÃǪ¸®³î, Ä¡¿ÀǪ¸®³îÀº ÀÌ ¾àÀÇ ´ë»ç¸¦ ¾ïÁ¦ÇϹǷΠº´¿ëÅõ¿©½Ã »ó¿ë·®ÀÇ 1/4·Î °¨·®ÇÑ´Ù. ÆäºÏ¼Ò½ºÅ¸Æ® ¶Ç´Â ±âŸ Å©»êƾ »êÈÈ¿¼Ò ¾ïÁ¦Á¦¿Í ÀÌ ¾àÀÇ º´¿ëÀº ±ÇÀåµÇÁö ¾Ê´Â´Ù. Å©»êƾ »êÈÈ¿¼Ò ÀúÇØÁ¦¸¦ Åõ¿©¹Þ°í TPMT Ȱ¼ºÀÌ ³·°Å³ª Á¸ÀçÇÏÁö ¾Ê´Â ȯÀÚ´Â Å©»êƾ »êÈÈ¿¼Ò ¹× TPMT ºñȰ¼º °æ·Î°¡ ¸ðµÎ ¿µÇâÀ» ¹Þ±â ¶§¹®¿¡ Ãß°¡ÀûÀÎ ¿ë·® °¨¼Ò ¶Ç´Â ´ëüġ·á°¡ ±ÇÀåµÈ´Ù.
2) ¼¼Æ÷µ¶¼ºÁ¦Á¦ ¶Ç´Â °ñ¼ö ¾ïÁ¦ ÀÛ¿ëÀ» °®´Â ¾à(Æä´Ï½Ç¶ó¹Î µî)°ú´Â º´¿ëÅõ¿©ÇÏÁö ¾Ê´Â´Ù.
3) ½Ã¸ÞƼµò, Àεµ¸ÞŸ½Å°ú º´¿ëÅõ¿©½Ã °ñ¼ö ¾ïÁ¦ È¿°ú°¡ Áõ°µÉ ¼ö ÀÖ´Ù.
4) ½Å°æ±ÙÂ÷´ÜÁ¦¿Í º´¿ë Åõ¿© ½Ã Ưº°ÇÑ ÁÖÀǰ¡ ÇÊ¿äÇÏ´Ù. ÀÌ ¾àÀº Å¥¶ó·¹, d-Æ©º¸Å¥¶ó¸°, ÆÇÅ©·Î´Ï¿ò, ¾ÆÆ®¶óÄí·ý, ·ÎÄí·Î´½, ½Ã½º¾ÆÆ®¶óÄí·ý°ú °°Àº ºñÅ»ºÐ±Ø¼º ±ÙÀÌ¿ÏÁ¦ÀÇ Å»ºÐ±Ø ¾ïÁ¦È¿°ú¿¡ ±æÇ×ÀÛ¿ëÀ» ÇÑ´Ù. ¼®½Ã´ÒÄݸ°°ú °°Àº Å»ºÐ±Ø¼º ±ÙÀÌ¿ÏÁ¦¿¡ ÀÇÇÑ ½Å°æ±Ù Â÷´ÜÀ» Áõ°½ÃŰ´Â °ÍÀ¸·Î ³ªÅ¸³µ´Ù. ¸¶Ãë°úÀÇ»ç´Â ¼ö¼ú Àü¿¡ ¾ÆÀÚÆ¼¿ÀÇÁ¸° Åõ¿© ¿©ºÎ¸¦ È®ÀÎÇØ¾ßÇÑ´Ù.
5) ¹éÇ÷±¸ Çü¼º¿¡ ¿µÇâÀ» ¹ÌÄ¥ ¼ö ÀÖ´Â ¾à(Æ®¸®¸ñ»çÁ¹·ù)°ú º´¿ëÅõ¿©½Ã ƯÈ÷ ½ÅÀåÀÌ½Ä È¯ÀÚ¿¡°Ô ¹éÇ÷±¸°¨¼ÒÁõÀÌ ³ªÅ¸³¯ ¼ö ÀÖ´Ù.
6) ÀÌ ¾àÀ» Åõ¿©ÁßÀΠȯÀÚÀÇ °íÇ÷¾Ð¿¡ ¾ÈÁö¿ÀÅٽŠÀüȯȿ¼Ò(ACE) ÀúÇØÁ¦¸¦ Åõ¿©ÇßÀ» ¶§ ºóÇ÷, ÁßÁõÀÇ ¹éÇ÷±¸ °¨¼ÒÁõÀÌ º¸°íµÇ¾ú´Ù.
7) ÀÌ ¾àÀº ¿Í¸£ÆÄ¸°ÀÇ Ç×ÀÀ°í È¿°ú¸¦ °¨¼Ò½ÃŰ¹Ç·Î º´¿ëÇÏ´Â °æ¿ì ÀÀ°í´ÉÀÇ º¯µ¿¿¡ ÁÖÀÇÇÑ´Ù.
8) »çÀÌŬ·Î½ºÆ÷¸° ¹× ¾àµ¶È »ý¹é½Å°ú º´¿ëÅõ¿©½Ã ÁÖÀÇÇÑ´Ù.
9) Æ®¸®¸ÞÅäÇÁ¸² ¹× ¼³ÆÄ¸ÞÅå»çÁ¹°ú º´¿ëÅõ¿©½Ã Ç×±Õ ´É·ÂÀÌ °ÈµÇ¾î »ý¸²ÇÁ¾× Á¢Á¾ÀÌ ºÒ°¡´ÉÇØÁø´Ù.
10) ÀÌ ¾à°ú ÄÚ¸£Æ¼ÄÚ½ºÅ×·ÎÀ̵带 º´¿ëÅõ¿©¹Þ´Â ȯÀÚ¿¡°Ô »ç¹é½Å°ú BÇü °£¿°¹é½ÅÀÇ Åõ¿©½Ã ±× È¿°ú°¡ °¨¼ÒµÈ °æ¿ì°¡ ÀÖ´Ù´Â º¸°í°¡ ÀÖ´Ù.
11) in vitro ½ÃÇè¿¡¼ ¾Æ¹Ì³ë»ì¸®½Ç·¹ÀÌÆ® À¯µµÃ¼(¿Ã»ì¶óÁø, ¸Þ»ì¶óÁø, ¼³ÆÄ»ì¶óÁø µî)´Â TPMT ÀúÇØÀÛ¿ëÀÌ º¸°íµÇ¾î ÀÖÀ¸¹Ç·Î ÀÌ ¾àÀ» Åõ¿©¹Þ°í Àִ ȯÀÚ¿¡°Ô º´¿ëÅõ¿©½Ã ÁÖÀÇÇÑ´Ù.
12) in vitro ½ÃÇè¿¡¼ Ǫ·Î¼¼¹Ìµå´Â Àΰ£ °£¼¼Æ÷¿¡¼ ¾ÆÀÚÄ¡¿ÀÇÁ¸°ÀÇ ´ë»ç¸¦ °¨¼Ò½ÃŲ´Ù. ÀÓ»óÀû ÀÇÀÇ´Â ¾ø´Ù. |
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2) ÀÌ ¾à 150mg°ú ÇÁ·¹µå´Ï¼Õ 30mgÀ» Åõ¿©ÇßÀ» ¶§ žƿ¡°Ô ¸²ÇÁ±¸°¨¼ÒÁõ, IgG ¹× IgMÀÇ °¨¼Ò, CMV °¨¿°, Èä¼± À½¿µÀÇ °¨¼Ò°¡ ³ªÅ¸³µ´Ù. ÀÌ ¾à 125mg°ú ÇÁ·¹µå´Ï¼Õ 12.5mgÀ» ÀӺο¡°Ô ¸ÅÀÏ Åõ¿©ÇßÀ» ¶§ ¹üÇ÷±¸ °¨¼ÒÁõ°ú ÁßÁõÀÇ ¸é¿ª°áÇÌÀÌ º¸°íµÇ¾ú´Ù. ÀÌ ¾à 200mg°ú ÇÁ·¹µå´Ï¼Õ 20mgÀ» °ÝÀÏ·Î ÀӽűⰣ ³»³» Åõ¿©ÇßÀ» ¶§ ÃàÀü¹æ¿¡ Á¤Çü ÀÌ»óÀÌ ÀÖ´Â ±âÇü¾Æ°¡ ž´Ù.
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2) °úüÁß ¼Ò¾ÆÀÇ °æ¿ì ±ÇÀå ¿ë·® ¹üÀ§ ³»ÀÇ ÃÖ°í ¿ë·®À» °í·ÁÇÒ ¼ö ÀÖ´Ù. ¶ÇÇÑ Ä¡·á °æ°ú¿¡ ´ëÇÑ ¸é¹ÐÇÑ ¸ð´ÏÅ͸µÀÌ ¿ä±¸µÈ´Ù.
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Azathioprine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Azathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. The mechanism of action of azathioprine in rheumatoid arthritis is not known but is most likely related to its immunosuppresive action.
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| Pharmacology |
Azathioprine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.
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Azathioprine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Thiopurine S-methyltransferase
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| Protein Binding |
Azathioprine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Azathioprine and the metabolite mercaptopurine are moderately bound to serum proteins (30%).
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| Half-life |
Azathioprine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Approximately 5 hours for the unchanged drug and its metabolites.
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| Absorption |
Azathioprine¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed following oral administration.
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| Pharmacokinetics |
AzathioprineÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
- Èí¼ö : Àß Èí¼öµÊ
- ºÐÆ÷ : ÅÂ¹Ý Åë°ú
- ´Ü¹é°áÇÕ : 30%
- ´ë»ç : °£ÀÇ xanthine oxidase¿¡ ÀÇÇØ Ȱ¼ºÇüÀÎ 6-mercaptopurineÀ¸·Î ¸¹Àº ¾çÀÌ ´ë»çµÊ
- ¹Ý°¨±â : ¸»±â ½ÅºÎÀü ȯÀÚ¿¡¼´Â ¾à°£ ¿¬ÀåµÊ
- Azathioprine : 12ºÐ
- 6-Mercaptopurine : 0.7-3 ½Ã°£
- ¼Ò½Ç : ¼Ò·®ÀÌ ¹Ìº¯Èü·Î ½Å¹è¼³µÇ¸ç, ´ë»çü´Â ÁÖ·Î ½Å¹è¼³µÊ
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| Biotransformation |
Azathioprine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid.
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| Toxicity |
Azathioprine¿¡ ´ëÇÑ Toxicity Á¤º¸ The oral LD50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.
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| Drug Interactions |
Azathioprine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Allopurinol Allopurinol increases the effect of thiopurineAnisindione The thiopurine decreases the anticoagulant effectAtracurium The agent decreases the effect of the muscle relaxantDicumarol The thiopurine decreases the anticoagulant effectDoxacurium The agent decreases the effect of the muscle relaxantGallamine Triethiodide The agent decreases the effect of the muscle relaxantMesalazine The 5-ASA derivative increases the toxicity of thiopurineMetocurine The agent decreases the effect of the muscle relaxantMivacurium The agent decreases the effect of the muscle relaxantAcenocoumarol The thiopurine decreases the anticoagulant effectOlsalazine The 5-ASA derivative increases the toxicity of thiopurinePancuronium The agent decreases the effect of the muscle relaxantSulfasalazine The 5-ASA derivative increase the toxicity of thiopurineTubocurarine The agent decreases the effect of the muscle relaxantVecuronium The agent decreases the effect of the muscle relaxantWarfarin The thiopurine decreases the anticoagulant effect
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸]
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| Food Interaction |
Azathioprine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with food to reduce irritation.
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| Drug Target |
[Drug Target]
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| Description |
Azathioprine¿¡ ´ëÇÑ Description Á¤º¸ An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)
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| Dosage Form |
Azathioprine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Powder, for solution IntravenousTablet Oral
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| Drug Category |
Azathioprine¿¡ ´ëÇÑ Drug_Category Á¤º¸ AntimetabolitesAntimetabolites, AntineoplasticAntirheumatic AgentsImmunosuppressive Agents
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| Smiles String Canonical |
Azathioprine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O
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| Smiles String Isomeric |
Azathioprine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O
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| InChI Identifier |
Azathioprine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C9H7N7O2S/c1-15-4-14-7(16(17)18)9(15)19-8-5-6(11-2-10-5)12-3-13-8/h2-4H,1H3,(H,10,11,12,13)/f/h10H
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| Chemical IUPAC Name |
Azathioprine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 6-(3-methyl-5-nitroimidazol-4-yl)sulfanyl-7H-purine
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| Drug-Induced Toxicity Related Proteins |
AZATHIOPRINE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Thiopurine S-methyltransferase Drug:azathioprine Toxicity:decrease in VCS-responsive cells. [¹Ù·Î°¡±â] Replated Protein:Purine nucleoside phosphorylase Drug:azathioprine Toxicity:bone marrow toxicity. [¹Ù·Î°¡±â] Replated Protein:Inosine triphosphate pyrophosphatase Drug:azathioprine Toxicity:adverse drug reactions to azathioprine therapy. [¹Ù·Î°¡±â] Replated Protein:5'-nucleotidase Drug:azathioprine Toxicity:bone marrow toxicity. [¹Ù·Î°¡±â] Replated Protein:Thiopurine S-methyltransferase Drug:azathioprine Toxicity:bone marrow toxicity. [¹Ù·Î°¡±â]
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