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1) ¼ºÀÎ : ÀÌ ¾àÀ¸·Î ÀüȯÇϱâ Àü¿¡ ¸ÕÀú ĵ¥»ç¸£Åº½Ç·º¼¼Æ¿ÀÇ ¿ë·®À» Á¶ÀýÇØ º¸¾Æ¾ß ÇÑ´Ù. ÀÓ»óÀûÀ¸·Î ÀûÀýÇÒ ¶§¿¡´Â ´ÜÀÏ¿ä¹ýÀ¸·ÎºÎÅÍ ÀÌ ¾àÀ¸·Î Á÷Á¢ÀûÀÎ ÀüȯÀ» °í·ÁÇÒ ¼ö ÀÖ´Ù. Ç×°íÇ÷¾ÐÈ¿°ú´Â ´ëºÎºÐ Åõ¿©½ÃÀÛ 4ÁÖ À̳»¿¡ ¾ò¾îÁø´Ù.
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4) ½ÅÀå¾Ö ȯÀÚ : Å©·¹¾ÆÆ¼´Ñ û¼ÒÀ²ÀÌ 30-80ml/min/1.73§³ BSAÀÎ °æÁõ¿¡¼ Áߵ ½ÅÀå¾Ö ȯÀÚ¿¡¼´Â ÀÌ ¾àÀ¸·Î ÀüȯÇϱâ Àü¿¡ ¸ÕÀú ĵ¥»ç¸£Åº½Ç·º¼¼Æ¿ÀÇ ¿ë·®Á¶ÀýÀ» °í·ÁÇÑ´Ù(ÀÌ·¯ÇÑ È¯ÀÚ¿¡¼ ĵ¥»ç¸£Åº½Ç·º¼¼Æ¿ÀÇ Ãʱâ¿ë·®Àº 4¹Ð¸®±×·¥ÀÌ´Ù). ÁßÁõ ½ÅÀå¾Ö ȯÀÚ(Å©·¹¾ÆÆ¼´Ñ û¼ÒÀ² 30ml/mim/1.73§³ BSA ¹Ì¸¸)¿¡°Ô´Â Åõ¿©ÇÏÁö ¾Ê´Â´Ù
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3) ±Þ¼º ¶Ç´Â ÁßÁõÀÇ ½ÅÀå¾Ö ȯÀÚ(Å©·¹¾ÆÆ¼´Ñ û¼ÒÀ²ÀÌ 30ml/min/1.73m2 BSA ¹Ì¸¸)
4) ÁßÁõ °£Àå¾Ö ȯÀÚ ¶Ç´Â ´ãÁóÁ¤Ã¼ ȯÀÚ
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6) ÅëdzȯÀÚ
7) ¿ø¹ß¼º °í¾Ëµµ½ºÅ×·ÐÇ÷Áõ ȯÀÚ(ÀÌ ¾à¹°¿¡ Àß ¹ÝÀÀÇÏÁö ¾Ê´Â´Ù.)
8) ¹«´¢ ȯÀÚ
9) Àú³ªÆ®·ý¡¤ÀúÄ®·ýÇ÷Áõ, °íÄ®½·Ç÷Áõ ȯÀÚ
10) ¾Öµð½¼º´ ȯÀÚ
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12) ÀÌ ¾àÀº À¯´çÀ» ÇÔÀ¯Çϰí ÀÖÀ¸¹Ç·Î, °¥¶ôÅä¿À½º ºÒ³»¼º(galactose intolerance), Lapp À¯´çºÐÇØÈ¿¼Ò °áÇÌÁõ(Lapp lactase deficiency) ¶Ç´Â Æ÷µµ´ç-°¥¶ôÅä¿À½º Èí¼öÀå¾Ö(glucose-galactose malabsorption) µîÀÇ À¯ÀüÀûÀÎ ¹®Á¦°¡ Àִ ȯÀÚ¿¡°Ô´Â Åõ¿©ÇÏ¸é ¾È µÈ´Ù.
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2) ü¾× ¹× ÀüÇØÁú ±ÕÇüÀÇ ÀÛÀº º¯È°¡ °£¼ºÈ¥¼ö¸¦ À¯¹ßÇÒ ¼ö ÀÖÀ¸¹Ç·Î Ƽ¾ÆÁöµå°è´Â °£Àå¾Ö ȯÀÚ³ª ÁøÇ༺ °£ÁúȯÀÌ Àִ ȯÀÚ¿¡°Ô Åõ¿©½Ã ÁÖÀǸ¦ ¿äÇÑ´Ù. °£ºÎÀü ȯÀÚ¿¡°Ô ÀÌ ¾àÀ» Åõ¿©ÇÑ °æÇèÀº ¾ø´Ù.
3) ´ëµ¿¸ÆÆÇ ¹× ½Â¸ðÆÇ ÇùÂøÁõ(ºñÈļº Æó¼â¼º ½É±Ùº´Áõ) : ´Ù¸¥ Ç÷°üÈ®ÀåÁ¦¿Í °°ÀÌ Ç÷¿ªÇÐÀûÀ¸·Î °ü·Ã ÀÖ´Â ´ëµ¿¸ÆÆÇ ¶Ç´Â ½Â¸ðÆÇ ÇùÂøÁõÀ̳ª ºñÈÄÇü Æó¼â¼º ½É±Ùº´Áõ ȯÀÚ¿¡°Ô Ưº°ÇÑ ÁÖÀǰ¡ ¿ä±¸µÈ´Ù.
4) °íÄ®·ýÇ÷Áõ ȯÀÚ(Áõ»óÀ» ¾ÇȽÃų ¼ö ÀÖ´Ù)
5) ½ÉÇÑ °üµ¿¸Æ°æÈÁõ ¶Ç´Â ³úµ¿¸Æ°æÈÁõ ȯÀÚ(±Þ°ÝÇÑ ÀÌ´¢°¡ ³ªÅ¸³¯ °æ¿ì, ±Þ¼ÓÇÑ Ç÷Àå·® °¨¼Ò·Î Ç÷¾×³óÃàÀ» ÀÏÀ¸ÄÑ Ç÷Àü»öÀüÁõÀÌ ³ªÅ¸³¯ ¼ö ÀÖ´Ù.)
6) ±³°¨½Å°æÀýÁ¦ÈÄÀÇ È¯ÀÚ(ÀÌ ¾àÀÇ Ç÷¾Ð°ÇÏÀÛ¿ëÀÌ Áõ°¡ÇÒ ¼ö ÀÖ´Ù.)
7) ½Åµ¿¸ÆÇùÂøÁõȯÀÚ(½ÅÇ÷·ù·®ÀÇ °¨¼Ò³ª »ç±¸Ã¼¿©°ú¾ÐÀÇ ÀúÇÏ¿¡ ÀÇÇØ ±Þ¼ÓÈ÷ ½Å±â´ÉÀ» ¾ÇȽÃų ¿ì·Á°¡ ÀÖ´Ù.)
8) ½ÅÀå¾Ö ȯÀÚ (¿ë¹ý¤ý¿ë·® Âü°í) ¶Ç´Â ½ÅÀå À̽ÄÀ» ÇÑ È¯ÀÚ
9) °£Àå¾Ö ȯÀÚ (¿ë¹ý¤ý¿ë·® Âü°í)
10) µð±âÅ»¸®½º, ´çÁúºÎ½ÅÇÇÁúÈ£¸£¸ó ¶Ç´Â ºÎ½ÅÇÇÁúÀÚ±ØÈ£¸£¸óÀÇ Åõ¿©¸¦ ¹Þ°í Àִ ȯÀÚ
11) ºÎ°©»ó¼±±â´ÉÇ×ÁøÁõ ȯÀÚ
12) ¿°Á¦ÇÑ¿ä¹ý ȯÀÚ
13) ¼³»ç, ±¸Åä ȯÀÚ
14) °í·ÉÀÚ
15) º»ÀÎ ¶Ç´Â ¾çÄ£À̳ª ÇüÁ¦¿¡ ÅëdzÀ̳ª ´ç´¢º´ÀÌ Àִ ȯÀÚ
16) ·¹´Ñ-¾ÈÁö¿ÀÅÙ½Å-¾Ëµµ½ºÅ׷аè(RAAS)ÀÇ ÀÌÁßÂ÷´Ü : ¾ÈÁö¿ÀÅٽŠII ¼ö¿ëü ±æÇ×Á¦(ARB), ACE¾ïÁ¦Á¦, ¶Ç´Â ¾Ë¸®½ºÅ°·» µî ·¹´Ñ-¾ÈÁö¿ÀÅÙ½Å-¾Ëµµ½ºÅ׷аè(RAAS)¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â ´Ù¸¥ ¾àÁ¦¿ÍÀÇ º´¿ëÀº ±ÇÀåµÇÁö ¾Ê´Â´Ù. ´ç´¢º´¼º ½ÅÀåÁúȯ ȯÀÚ¿¡¼ ACE¾ïÁ¦Á¦¿Í ¾ÈÁö¿ÀÅٽмö¿ëü ±æÇ×Á¦ÀÇ º´¿ëÀº ¾ÈµÈ´Ù.
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2) ½ÅÀå¾Ö/½ÅÀåÀ̽Ä: ÀÌ ¾àÀ» ½ÅÀå¾Ö ȯÀÚ¿¡°Ô Åõ¿©ÇÏ´Â °æ¿ì Ä®·ý, Å©·¹¾ÆÆ¼´Ñ, ¿ä»ê ¼öÄ¡¸¦ ÁÖ±âÀûÀ¸·Î ¸ð´ÏÅ͸µ Çϵµ·Ï ±ÇÀåÇÑ´Ù. ½ÅÀå À̽ÄÀ» ÇÑ È¯ÀÚ¿¡°Ô ÀÌ ¾àÀ» »ç¿ëÇÑ °æÇèÀº Á¦ÇÑÀûÀÌ´Ù.
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6) È÷µå·ÎŬ·Î·ÎƼ¾ÆÁöµå´Â ¿ë·®ÀÇÁ¸ÀûÀ¸·Î ´¢¿¡¼ Ä®·ý ¹è¼³À» Áõ°¡½ÃÄÑ ÀúÄ®·ýÇ÷ÁõÀ» ÀÏÀ¸Å³ ¼ö ÀÖ´Ù. ÀÌ·¯ÇÑ ÀÛ¿ëÀº ĵ¥»ç¸£Åº½Ç·º¼¼Æ¿°ú º´¿ëÇßÀ» ¶§ ´ú ¹ß»ýÇÏ´Â °Í °°´Ù. ÀúÄ®·ýÇ÷ÁõÀÇ À§ÇèÀº °£°æº¯È¯ÀÚ, ÀÌ´¢È¿°ú°¡ °ú´ÙÇÏ°Ô ³ªÅ¸³ª´Â ȯÀÚ, ÀüÇØÁúÀ» ºÎÀûÀýÇÏ°Ô ¼·ÃëÇÑ È¯ÀÚ, ÄÚ¸£Æ¼ÄÚ½ºÅ×·ÎÀ̵峪 ºÎ½ÅÇÇÁúÀÚ±ØÈ£¸£¸ó(ACTH)À» º´¿ëÇϴ ȯÀÚ¿¡¼ Áõ°¡µÉ ¼ö ÀÖ´Ù.
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(candesartan. ÀӽŠ2±â ¶Ç´Â 3±â Åõ¿©½Ã Dµî±Þ )
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Mechanism of Action
Candesartan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Candesartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance.Hydrochlorothiazide¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ As a diuretic, hydrochlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like hydrochlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of hydrochlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
Pharmacology
Candesartan¿¡ ´ëÇÑ Pharmacology Á¤º¸ Candesartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Unlike the angiotensin receptor antagonist losartan, Candesartan does not have an active metabolite or possess uricosuric effects.Hydrochlorothiazide¿¡ ´ëÇÑ Pharmacology Á¤º¸ Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+ /Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Metabolism
Candesartan¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 11B2 (CYP11B2)Hydrochlorothiazide¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Not Available
Protein Binding
Candesartan¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.Hydrochlorothiazide¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 67.9%
Half-life
Candesartan¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Approximately 9 hours.Hydrochlorothiazide¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 5.6 and 14.8 hours
Absorption
Candesartan¿¡ ´ëÇÑ Absorption Á¤º¸ Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan was estimated to be 15%. Food with a high fat content has no affect on the bioavailability of candesartan from candesartan cilexetil.Hydrochlorothiazide¿¡ ´ëÇÑ Absorption Á¤º¸ 50-60%
Pharmacokinetics
Candesartan cilexetilÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
¾àÈ¿ ¹ßÇö½Ã°£ : 2-4½Ã°£
ÃÖ°í È¿°ú ¹ßÇö½Ã°£ : 6-8 ½Ã°£
ÃÖ°í Ç÷Áß³óµµ µµ´Þ½Ã°£ : 3-4 ½Ã°£
¾àÈ¿ Áö¼Ó½Ã°£ : 24½Ã°£ ÀÌ»ó
»ýü³»ÀÌ¿ë·ü : 15%, À½½Ä¹°¿¡ ÀÇÇØ ¿µÇâÀ» ¹ÞÁö ¾ÊÀ½
ºÐÆ÷¿ëÀû : 0.13 L/kg
´Ü¹é°áÇÕ : 99 % ÀÌ»ó
´ë»ç : Candesartan cilexetilÀº Èí¼ö°úÁ¤¿¡¼ 99% ÀÌ»óÀÌ À§Àå°ü º®¿¡¼ Ȱ¼ºÇü ´ë»çüÀÎ candesartanÀ¸·Î ´ë»çµÊ
¹Ý°¨±â : CandesartanÀ¸·Î 5.1-10.5 ½Ã°£
¼Ò½Ç : CandesartanÀº °ÅÀÇ ¹Ìº¯Èü·Î 67% ´ëº¯, 33% ´¢¹è¼³
HydrochlorothiazideÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
ÀÌ´¢È¿°ú ¹ßÇö½Ã°£ : °æ±¸ : 2½Ã°£ À̳»
ÃÖ´ëÈ¿°ú ¹ßÇö½Ã°£ : 4½Ã°£
ÀÛ¿ëÁö¼Ó½Ã°£ : 6-12½Ã°£
Èí¼ö : °æ±¸ : 60-80%
¼Ò½Ç : ¹Ìº¯Èü·Î ½Å¹è¼³µÈ´Ù.
Biotransformation
Candesartan¿¡ ´ëÇÑ Biotransformation Á¤º¸ During absorption from the gastrointestinal tract, the prodrug candesartan cilexetil undergoes rapid and complete ester hydrolysis to form the active drug, candesartan. Elimination of candesartan is primarily as unchanged drug in the urine and, by the biliary route, in the feces. Minor hepatic metabolism of candesartan occurs by O -deethylation to form an inactive metabolite.Hydrochlorothiazide¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hydrochlorothiazide is not metabolized.
Toxicity
Candesartan¿¡ ´ëÇÑ Toxicity Á¤º¸ No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg.Hydrochlorothiazide¿¡ ´ëÇÑ Toxicity Á¤º¸ The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Drug Interactions
Candesartan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amiloride Increased risk of hyperkaliemiaDrospirenone Increased risk of hyperkaliemiaLithium The ARB increases serum levels of lithiumPotassium Increased risk of hyperkaliemiaSpironolactone Increased risk of hyperkaliemiaTriamterene Increased risk of hyperkaliemiaHydrochlorothiazide¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amantadine The diuretic increases the adverse effect of amantadineDeslanoside Possible electrolyte variations and arrhythmiasDigitoxin Possible electrolyte variations and arrhythmiasDigoxin Possible electrolyte variations and arrhythmiasLithium The thiazide diuretic increases serum levels of lithiumDofetilide Increased risk of cardiotoxicity and arrhythmiasDiazoxide Significant hyperglycemic effect
CYP450 Drug Interaction
[CYP450 TableÁ÷Á¢Á¶È¸]
Food Interaction
Candesartan¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Administer on a regular basis, at about the same time each day.Hydrochlorothiazide¿¡ ´ëÇÑ Food Interaction Á¤º¸ Avoid alcohol.Avoid excess salt/sodium unless otherwise instructed by your physician.Take with food.Increase potassium intake; add a banana or orange juice; unless instructed otherwise.Avoid natural licorice.Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Drug Target
[Drug Target]
Description
Candesartan¿¡ ´ëÇÑ Description Á¤º¸ Candesartan, a specific angiotensin II antagonist, is used alone or with other antihypertensive agents to treat hypertension. Candesartan competes with angiotensin II for binding at the AT1 receptor subtype. As angiotensin II is a vasoconstrictor which also stimulates the synthesis and release of aldosterone, blockage of its effects results in a decreases in systemic vascular resistance.Hydrochlorothiazide¿¡ ´ëÇÑ Description Á¤º¸ A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [PubChem]
Drug Category
Candesartan¿¡ ´ëÇÑ Drug_Category Á¤º¸ Angiotensin II Receptor AntagonistsAngiotensin II Type 1 Receptor BlockersAntihypertensive AgentsHydrochlorothiazide¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihypertensive AgentsDiureticsSodium Chloride Symporter Inhibitors
Smiles String Canonical
Candesartan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
Smiles String Isomeric
Candesartan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
InChI Identifier
Candesartan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29)/f/h28,31HHydrochlorothiazide¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)/f/h9H2
Chemical IUPAC Name
Candesartan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acidHydrochlorothiazide¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 6-chloro-1,1-dioxo-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide
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