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医薬品インタビューフォーム
2016 ᖺ 3 ᭶ᨵゞ㸦➨ 6 ∧㸧 ᪥ᮏᶆ‽ၟရศ㢮␒ྕ 873399 ་⸆ရࣥࢱࣅ࣮ࣗࣇ࢛࣮࣒ ᪥ᮏ㝔⸆ᖌࡢ IF グ㍕せ㡿 2013 ‽ᣐࡋ࡚సᡂ ᙧ ⣲㘄 〇 ࡢ つ ไ ༊ ศ ヱᙜࡋ࡞࠸ つ 㔞 50mg 㸸1 㘄୰᪥ᒁࢩࣟࢫࢱࢰ࣮ࣝ 50mg 100mg 㸸1 㘄୰᪥ᒁࢩࣟࢫࢱࢰ࣮ࣝ 100mg ྡ ྡ㸸ࢩࣟࢫࢱࢰ࣮ࣝ㸦JAN㸧 ὒྡ㸸Cilostazol㸦JAN㸪INN㸧 ୍ ᱁ ࣭ ⯡ ྵ 〇㐀㈍ᢎㄆᖺ᭶᪥ ⸆౯ᇶ‽㍕࣭Ⓨᖺ᭶᪥ 㛤Ⓨ࣭〇㐀㈍㸦㍺ධ㸧࣭ ᥦ ᦠ ࣭ ㈍ ♫ ྡ 50mg 100mg 〇㐀㈍ᢎㄆᖺ᭶᪥ 2009 ᖺ 7 ᭶ 13 ᪥ 2000 ᖺ 2 ᭶ 18 ᪥ ⸆౯ᇶ‽㍕ᖺ᭶᪥ 2009 ᖺ 11 ᭶ 13 ᪥ 2000 ᖺ 7 ᭶ 7 ᪥ Ⓨ ᖺ ᭶ 2009 ᖺ 11 ᭶ 13 ᪥ 2000 ᖺ 7 ᭶ 7 ᪥ 〇㐀㈍ඖ 㸸 ᪥ ᑑ〇⸆ᰴᘧ♫ ་⸆ရሗᢸᙜ⪅ࡢ㐃⤡ඛ ၥ ࠸ ྜ ࢃ ࡏ ❆ ཱྀ ᑑ〇⸆ᰴᘧ♫ TEL㸸0120-996-156 FAX㸸0268-82-2215 ࣮࣒࣮࣍࣌ࢪ URL: http://www.kotobuki-pharm.co.jp/ ᮏ IF ࡣ 2016 ᖺ 3 ᭶ᨵゞ㸦➨ 17 ∧㸧ࡢῧᩥ᭩ࡢグ㍕ᇶ࡙ࡁసᡂࡋࡓࠋ ᭱᪂ࡢῧᩥ᭩ሗࡣࠊ་⸆ရ་⒪ᶵჾሗᥦ౪࣮࣒࣮࣍࣌ࢪhttp://www.pmda.go.jp/࡚ࡈ☜ㄆࡃࡔࡉ࠸ࠋ IF⏝ࡢᡭᘬࡁࡢᴫせ 㸫᪥ᮏ㝔⸆ᖌ㸫 1㸬་⸆ရࣥࢱࣅ࣮ࣗࣇ࢛࣮࣒సᡂࡢ⤒⦋ ་⒪⏝་⸆ရࡢᇶᮏⓗ࡞せ⣙ሗࡋ࡚་⒪⏝་⸆ရῧᩥ᭩㸦௨ୗࠊῧᩥ᭩␎ࡍ㸧ࡀ࠶ࡿࠋ་⒪ ⌧ሙ࡛་ᖌ࣭⸆ᖌ➼ࡢ་⒪ᚑ⪅ࡀ᪥ᖖᴗົᚲせ࡞་⸆ရࡢ㐺ᛶ⏝ሗࢆά⏝ࡍࡿ㝿ࡣࠊῧᩥ ᭩グ㍕ࡉࢀࡓሗࢆࡅࡿ᭦ヲ⣽࡞ሗࡀᚲせ࡞ሙྜࡀ࠶ࡿࠋ ་⒪⌧ሙ࡛ࡣࠊᙜヱ་⸆ရࡘ࠸࡚〇⸆ᴗࡢ་⸆ရሗᢸᙜ⪅➼ሗࡢ㏣ຍㄳồࡸ㉁ࢆࡋ࡚ሗ ࢆ⿵ࡋ࡚ᑐฎࡋ࡚ࡁ࡚࠸ࡿࠋࡇࡢ㝿ᚲせ࡞ሗࢆ⥙⨶ⓗධᡭࡍࡿࡓࡵࡢሗࣜࢫࢺࡋ࡚ࣥࢱࣅ ࣮ࣗࣇ࢛࣮࣒ࡀㄌ⏕ࡋࡓࠋ 63ᖺ᪥ᮏ㝔⸆ᖌ㸦௨ୗࠊ᪥⸆␎ࡍ㸧Ꮫ⾡➨2ᑠጤဨࡀࠕ་⸆ရࣥࢱࣅ࣮ࣗࣇ࢛࣮ ࣒ࠖ 㸦௨ୗࠊIF␎ࡍ㸧ࡢ⨨ࡅ୪ࡧ IFグ㍕ᵝᘧࢆ⟇ᐃࡋࡓࠋࡑࡢᚋࠊ་⒪ᚑ⪅ྥࡅ୪ࡧᝈ⪅ྥ ࡅ་⸆ရሗࢽ࣮ࢬࡢኚࢆཷࡅ࡚ࠊᖹᡂ10ᖺ9᭶᪥⸆Ꮫ⾡➨3ᑠጤဨ࠾࠸࡚ IFグ㍕せ㡿ࡢᨵゞ ࡀ⾜ࢃࢀࡓࠋ ᭦10ᖺࡀ⤒㐣ࡋࡓ⌧ᅾࠊ་⸆ရሗࡢࡾᡭ࡛࠶ࡿ〇⸆ᴗࠊ࠸ᡭ࡛࠶ࡿ་⒪⌧ሙࡢ⸆ᖌࠊ᪉ ࡗ࡚⸆࣭་⒪⎔ቃࡣࡁࡃኚࡋࡓࡇࢆཷࡅ࡚ࠊᖹᡂ20ᖺ9᭶᪥⸆་⸆ሗጤဨ࠾࠸࡚ ᪂ࡓ࡞IFグ㍕せ㡿ࡀ⟇ᐃࡉࢀࡓࠋ IFグ㍕せ㡿2008࡛ࡣࠊIFࢆ⣬፹యࡢᏊࡋ࡚ᥦ౪ࡍࡿ᪉ᘧࡽࠊPDF➼ࡢ㟁☢ⓗࢹ࣮ࢱࡋ࡚ᥦ౪ ࡍࡿࡇ㸦e-IF㸧ࡀཎ๎࡞ࡗࡓࠋࡇࡢኚ᭦࠶ࢃࡏ࡚ࠊῧᩥ᭩࠾࠸࡚ࠕຠ⬟࣭ຠᯝࡢ㏣ຍࠖࠊ ࠕ㆙࿌࣭ ⚗ᚷ࣭㔜せ࡞ᇶᮏⓗὀពࡢᨵゞࠖ࡞ࡢᨵゞࡀ࠶ࡗࡓሙྜࠊᨵゞࡢ᰿ᣐࢹ࣮ࢱࢆ㏣ຍࡋࡓ᭱᪂∧ࡢe-IF ࡀᥦ౪ࡉࢀࡿࡇ࡞ࡗࡓࠋ ᭱ ᪂ ∧ ࡢ e-IF ࡣ ࠊ㸦 ⊂ 㸧 ་ ⸆ ရ ་ ⒪ ᶵ ჾ ⥲ ྜ ᶵ ᵓ ࡢ ་ ⸆ ရ ሗ ᥦ ౪ ࣍ ࣮ ࣒ ࣌ ࣮ ࢪ 㸦http://www.info.pmda.go.jp/㸧ࡽ୍ᣓࡋ࡚ධᡭྍ⬟࡞ࡗ࡚࠸ࡿࠋ᪥ᮏ㝔⸆ᖌ࡛ࡣࠊe-IFࢆᥖ㍕ ࡍࡿ་⸆ရሗᥦ౪࣮࣒࣮࣍࣌ࢪࡀබᘧࢧࢺ࡛࠶ࡿࡇ㓄៖ࡋ࡚ࠊ⸆౯ᇶ‽㍕࠶ࢃࡏ࡚e-IFࡢ ሗࢆ᳨ウࡍࡿ⤌⧊ࢆタ⨨ࡋ࡚ࠊಶࠎࡢIFࡀῧᩥ᭩ࢆ⿵ࡍࡿ㐺ṇ⏝ሗࡋ࡚㐺ษᑂᰝ᳨࣭ウࡍࡿ ࡇࡋࡓࠋ 2008ᖺࡼࡾᖺ4ᅇࡢࣥࢱࣅ࣮ࣗࣇ᳨࢛࣮࣒ウࢆ㛤ദࡋࡓ୰࡛ᣦࡋ࡚ࡁࡓ㡯ࢆホ౯ࡋࠊ〇⸆ ᴗࡗ࡚ࡶࠊ་ᖌ࣭⸆ᖌ➼ࡗ࡚ࡶࠊຠ⋡ࡢⰋ࠸ሗ※ࡍࡿࡇࢆ⪃࠼ࡓࠋࡑࡇ࡛⯡ࠊIFグ㍕ せ㡿ࡢ୍㒊ᨵゞࢆ⾜࠸IFグ㍕せ㡿2013ࡋ࡚බ⾲ࡍࡿ㐠ࡧ࡞ࡗࡓࠋ 2㸬IFࡣ IFࡣࠕῧᩥ᭩➼ࡢሗࢆ⿵ࡋࠊ⸆ᖌ➼ࡢ་⒪ᚑ⪅ࡗ࡚᪥ᖖᴗົᚲせ࡞ࠊ་⸆ရࡢရ㉁⟶ ⌮ࡢࡓࡵࡢሗࠊฎ᪉タィࡢࡓࡵࡢሗࠊㄪࡢࡓࡵࡢሗࠊ་⸆ရࡢ㐺ᛶ⏝ࡢࡓࡵࡢሗࠊ⸆Ꮫⓗ࡞ ᝈ⪅ࢣࡢࡓࡵࡢሗ➼ࡀ㞟⣙ࡉࢀࡓ⥲ྜⓗ࡞ಶูࡢ་⸆ရゎㄝ᭩ࡋ࡚ࠊ᪥⸆ࡀグ㍕せ㡿ࢆ⟇ᐃࡋࠊ ⸆ᖌ➼ࡢࡓࡵᙜヱ་⸆ရࡢ〇⸆ᴗసᡂཬࡧᥦ౪ࢆ౫㢗ࡋ࡚࠸ࡿᏛ⾡㈨ᩱࠖ⨨ࡅࡽࢀࡿࠋ ࡓࡔࡋࠊ⸆ἲ࣭〇⸆ᴗᶵᐦ➼㛵ࢃࡿࡶࡢࠊ〇⸆ᴗࡢ〇ດຊࢆ↓ຠࡍࡿࡶࡢཬࡧ⸆ᖌ⮬ࡽ ࡀホ౯ุ࣭᩿࣭ᥦ౪ࡍࡁ㡯➼ࡣIFࡢグ㍕㡯ࡣ࡞ࡽ࡞࠸ࠋゝ࠸࠼ࡿࠊ〇⸆ᴗࡽᥦ౪ࡉࢀࡓ IFࡣࠊ⸆ᖌ⮬ࡽࡀホ౯ุ࣭᩿࣭⮫ᗋ㐺ᛂࡍࡿࡶࠊᚲせ࡞⿵ࢆࡍࡿࡶࡢ࠸࠺ㄆ㆑ࢆᣢࡘࡇࢆ ๓ᥦࡋ࡚࠸ࡿࠋ 㹙IFࡢᵝᘧ㹛 ձつ᱁ࡣA4∧ࠊᶓ᭩ࡁࡋࠊཎ๎ࡋ࡚9࣏ࣥࢺ௨ୖࡢᏐయ㸦ᅗ⾲ࡣ㝖ࡃ㸧࡛グ㍕ࡋࠊ୍Ⰽๅࡾࡍࡿࠋ ࡓࡔࡋࠊῧᩥ᭩࡛㉥ᯟ࣭㉥Ꮠࢆ⏝࠸ࡓሙྜࡣࠊ㟁Ꮚ፹య࡛ࡣࡇࢀᚑ࠺ࡢࡶࡍࡿࠋ ղIFグ㍕せ㡿ᇶ࡙ࡁసᡂࡋࠊྛ㡯┠ྡࡣࢦࢩࢵࢡయ࡛グ㍕ࡍࡿࠋ ճ⾲⣬ࡢグ㍕ࡣ⤫୍ࡋࠊ⾲⣬⥆ࡅ࡚᪥⸆సᡂࡢࠕIF⏝ࡢᡭᘬࡁࡢᴫせࠖࡢᩥࢆグ㍕ࡍࡿࡶࡢࡋࠊ 2㡫ࡲࡵࡿࠋ 㹙IFࡢసᡂ㹛 ձIFࡣཎ๎ࡋ࡚〇ࡢᢞ⤒㊰ู㸦ෆ⏝ࠊὀᑕࠊእ⏝㸧సᡂࡉࢀࡿࠋ ղIFグ㍕ࡍࡿ㡯┠ཬࡧ㓄ิࡣ᪥⸆ࡀ⟇ᐃࡋࡓIFグ㍕せ㡿‽ᣐࡍࡿࠋ ճῧᩥ᭩ࡢෆᐜࢆ⿵ࡍࡿࡢIFࡢ᪨ἢࡗ࡚ᚲせ࡞ሗࡀグ㍕ࡉࢀࡿࠋ մ〇⸆ᴗࡢᶵᐦ➼㛵ࡍࡿࡶࡢࠊ〇⸆ᴗࡢ〇ດຊࢆ↓ຠࡍࡿࡶࡢཬࡧ⸆ᖌࢆࡣࡌࡵ་⒪ᚑ⪅ ⮬ࡽࡀホ౯ุ࣭᩿࣭ᥦ౪ࡍࡁ㡯ࡘ࠸࡚ࡣグ㍕ࡉࢀ࡞࠸ࠋ յࠕ་⸆ရࣥࢱࣅ࣮ࣗࣇ࢛࣮࣒グ㍕せ㡿2013ࠖ㸦௨ୗࠊࠕIFグ㍕せ㡿2013ࠖ␎ࡍ㸧ࡼࡾసᡂࡉࢀࡓIF ࡣࠊ㟁Ꮚ፹య࡛ࡢᥦ౪ࢆᇶᮏࡋࠊᚲせᛂࡌ࡚⸆ᖌࡀ㟁Ꮚ፹య㸦PDF㸧ࡽ༳ๅࡋ࡚⏝ࡍࡿࠋ ᴗ࡛ࡢ〇ᮏࡣᚲ㡲࡛ࡣ࡞࠸ࠋ 㹙IFࡢⓎ⾜㹛 ձࠕIFグ㍕せ㡿2013ࠖࡣࠊᖹᡂ25ᖺ10᭶௨㝆ᢎㄆࡉࢀࡓ᪂་⸆ရࡽ㐺⏝࡞ࡿࠋ ղୖグ௨እࡢ་⸆ရࡘ࠸࡚ࡣࠊ ࠕIFグ㍕せ㡿2013ࠖࡼࡿసᡂ࣭ᥦ౪ࡣᙉไࡉࢀࡿࡶࡢ࡛ࡣ࡞࠸ࠋ ճ⏝ୖࡢὀពࡢᨵゞࠊᑂᰝ⤖ᯝཪࡣホ౯⤖ᯝ㸦⮫ᗋホ౯㸧ࡀබ⾲ࡉࢀࡓⅬ୪ࡧ㐺ᛂࡢᣑ ➼ࡀ࡞ࡉࢀࠊグ㍕ࡍࡁෆᐜࡀࡁࡃኚࢃࡗࡓሙྜࡣIFࡀᨵゞࡉࢀࡿࠋ 3㸬IFࡢ⏝࠶ࡓࡗ࡚ ࠕIFグ㍕せ㡿2013ࠖ࠾࠸࡚ࡣࠊPDFࣇࣝࡼࡿ㟁Ꮚ፹య࡛ࡢᥦ౪ࢆᇶᮏࡋ࡚࠸ࡿࠋሗࢆ⏝ ࡍࡿ⸆ᖌࡣࠊ㟁Ꮚ፹యࡽ༳ๅࡋ࡚⏝ࡍࡿࡇࡀཎ๎࡛࠶ࡿࠋ 㟁Ꮚ፹యࡢIFࡘ࠸࡚ࡣࠊ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓࡢ་⸆ရ་⒪ᶵჾሗᥦ౪࣮࣒࣮࣍࣌ࢪᥖ㍕ሙᡤ ࡀタᐃࡉࢀ࡚࠸ࡿࠋ 〇⸆ᴗࡣࠕ་⸆ရࣥࢱࣅ࣮ࣗࣇ࢛࣮࣒సᡂࡢᡭᘬࡁࠖᚑࡗ࡚సᡂ࣭ᥦ౪ࡍࡿࡀࠊIFࡢཎⅬࢆ㋃ࡲ ࠼ࠊ་⒪⌧ሙ㊊ࡋ࡚࠸ࡿሗࡸIFసᡂグ㍕ࡋ㞴࠸ሗ➼ࡘ࠸࡚ࡣ〇⸆ᴗࡢMR➼ࡢࣥࢱࣅ ࣮ࣗࡼࡾ⸆ᖌ➼⮬ࡽࡀෆᐜࢆᐇࡉࡏࠊIFࡢ⏝ᛶࢆ㧗ࡵࡿᚲせࡀ࠶ࡿࠋࡲࡓࠊ㝶ᨵゞࡉࢀࡿ⏝ ୖࡢὀព➼㛵ࡍࡿ㡯㛵ࡋ࡚ࡣࠊIFࡀᨵゞࡉࢀࡿࡲ࡛ࡢ㛫ࡣࠊᙜヱ་⸆ရࡢ〇⸆ᴗࡀᥦ౪ࡍࡿῧ ᩥ᭩ࡸ࠾▱ࡽࡏᩥ᭩➼ࠊ࠶ࡿ࠸ࡣ་⸆ရ་⒪ᶵჾሗ㓄ಙࢧ࣮ࣅࢫ➼ࡼࡾ⸆ᖌ➼⮬ࡽࡀᩚഛࡍࡿ ࡶࠊIFࡢ⏝࠶ࡓࡗ࡚ࡣࠊ᭱᪂ࡢῧᩥ᭩ࢆ་⸆ရ་⒪ᶵჾሗᥦ౪࣮࣒࣮࣍࣌ࢪ࡛☜ㄆࡍࡿࠋ ࡞࠾ࠊ㐺ṇ⏝ࡸᏳᛶࡢ☜ಖࡢⅬࡽグ㍕ࡉࢀ࡚࠸ࡿࠕ⮫ᗋᡂ⦼ࠖࡸࠕ࡞እᅜ࡛ࡢⓎ≧ἣࠖ㛵 ࡍࡿ㡯┠➼ࡣᢎㄆ㡯㛵ࢃࡿࡇࡀ࠶ࡾࠊࡑࡢྲྀᢅ࠸ࡣ༑ศ␃ពࡍࡁ࡛࠶ࡿࠋ 4㸬⏝㝿ࡋ࡚ࡢ␃ពⅬ IFࢆ⸆ᖌ➼ࡢ᪥ᖖᴗົ࠾࠸࡚Ḟࡍࡇࡀ࡛ࡁ࡞࠸་⸆ရሗ※ࡋ࡚ά⏝ࡋ࡚㡬ࡁࡓ࠸ࠋࡋࡋࠊ ⸆ἲࡸ་⒪⏝་⸆ရࣉ࣮ࣟࣔࢩࣙࣥࢥ࣮ࢻ➼ࡼࡿつไࡼࡾࠊ〇⸆ᴗࡀ་⸆ရሗࡋ࡚ᥦ౪࡛ࡁ ࡿ⠊ᅖࡣ⮬ࡎ㝈⏺ࡀ࠶ࡿࠋIFࡣ᪥⸆ࡢグ㍕せ㡿ࢆཷࡅ࡚ࠊᙜヱ་⸆ရࡢ〇⸆ᴗࡀసᡂ࣭ᥦ౪ࡍࡿ ࡶࡢ࡛࠶ࡿࡇࡽࠊグ㍕࣭⾲⌧ࡣไ⣙ࢆཷࡅࡊࡿࢆᚓ࡞࠸ࡇࢆㄆ㆑ࡋ࡚࠾࡞ࡅࢀࡤ࡞ࡽ࡞࠸ࠋ ࡲࡓ〇⸆ᴗࡣࠊIFࡀ࠶ࡃࡲ࡛ࡶῧᩥ᭩ࢆ⿵ࡍࡿሗ㈨ᮦ࡛࠶ࡾࠊᚋࣥࢱ࣮ࢿࢵࢺ࡛ࡢබ㛤➼ ࡶ㋃ࡲ࠼ࠊ⸆ἲୖࡢᗈ࿌つไゐࡋ࡞࠸ࡼ࠺␃ពࡋసᡂࡉࢀ࡚࠸ࡿࡇࢆ⌮ゎࡋ࡚ሗࢆά⏝ࡍࡿᚲ せࡀ࠶ࡿࠋ 㸦2013 ᖺ 4 ᭶ᨵゞ㸧 ┠ ḟ 㹇㸬ᴫせ㛵ࡍࡿ㡯┠ 㸯㸬㛤Ⓨࡢ⤒⦋ ------------------------------------------------------------------------------------------------------------------ 1 㸰㸬〇ရࡢ⒪Ꮫⓗ࣭〇Ꮫⓗ≉ᛶ --------------------------------------------------------------------------------------- 1 㹇㹇㸬ྡ⛠㛵ࡍࡿ㡯┠ 㸯.㈍ྡ 㸦㸯㸧ྡ ------------------------------------------------------------------------------------------------------------------------ 2 㸦㸰㸧ὒྡ ------------------------------------------------------------------------------------------------------------------------ 2 㸦㸱㸧ྡ⛠ࡢ⏤᮶ --------------------------------------------------------------------------------------------------------------- 2 㸰㸬୍⯡ྡ 㸦㸯㸧ྡ㸦ྡἲ㸧 --------------------------------------------------------------------------------------------------------- 2 㸦㸰㸧ὒྡ㸦ྡἲ㸧 --------------------------------------------------------------------------------------------------------- 2 㸦㸱㸧ࢫࢸ࣒ --------------------------------------------------------------------------------------------------------------------- 2 㸱㸬ᵓ㐀ᘧཪࡣ♧ᛶᘧ --------------------------------------------------------------------------------------------------------- 2 㸲㸬ศᏊᘧཬࡧศᏊ㔞 --------------------------------------------------------------------------------------------------------- 2 㸳㸬Ꮫྡ㸦ྡἲ㸧 --------------------------------------------------------------------------------------------------------- 2 㸴㸬័⏝ྡࠊูྡࠊ␎ྕࠊグྕ␒ྕ --------------------------------------------------------------------------------------- 2 㸵㸬CAS Ⓩ㘓␒ྕ -------------------------------------------------------------------------------------------------------------- 2 㹇㹇㹇㸬᭷ຠᡂศ㛵ࡍࡿ㡯┠ 㸯㸬≀⌮Ꮫⓗᛶ㉁ 㸦㸯㸧እほ࣭ᛶ≧ --------------------------------------------------------------------------------------------------------------- 3 㸦㸰㸧⁐ゎᛶ --------------------------------------------------------------------------------------------------------------------- 3 㸦㸱㸧྾‵ᛶ --------------------------------------------------------------------------------------------------------------------- 3 㸦㸲㸧⼥Ⅼ㸦ศゎⅬ㸧 ࠊἛⅬࠊจᅛⅬ ------------------------------------------------------------------------------------- 3 㸦㸳㸧㓟ሷᇶゎ㞳ᐃᩘ --------------------------------------------------------------------------------------------------------- 3 㸦㸴㸧ศ㓄ಀᩘ ------------------------------------------------------------------------------------------------------------------ 3 㸦㸵㸧ࡑࡢࡢ࡞♧ᛶ್ --------------------------------------------------------------------------------------------------- 3 㸰㸬᭷ຠᡂศࡢྛ✀᮲௳ୗ࠾ࡅࡿᏳᐃᛶ ------------------------------------------------------------------------------ 3 㸱㸬᭷ຠᡂศࡢ☜ㄆヨ㦂ἲ --------------------------------------------------------------------------------------------------- 3 㸲㸬᭷ຠᡂศࡢᐃ㔞ἲ --------------------------------------------------------------------------------------------------------- 3 㹇㹔㸬〇㛵ࡍࡿ㡯┠ 㸯㸬ᙧ 㸦㸯㸧ᙧࡢ༊ูࠊእほཬࡧᛶ≧ ------------------------------------------------------------------------------------------ 4 㸦㸰㸧〇ࡢ≀ᛶ --------------------------------------------------------------------------------------------------------------- 4 㸦㸱㸧㆑ูࢥ࣮ࢻ --------------------------------------------------------------------------------------------------------------- 4 㸦㸲㸧pHࠊᾐ㏱ᅽẚࠊ⢓ᗘࠊẚ㔜ࠊ↓⳦ࡢ᪨ཬࡧᏳᐃ࡞ pH ᇦ➼ ----------------------------------------------- 4 㸰㸬〇ࡢ⤌ᡂ 㸦㸯㸧᭷ຠᡂศ㸦άᛶᡂศ㸧ࡢྵ㔞 --------------------------------------------------------------------------------------- 4 㸦㸰㸧ῧຍ≀ --------------------------------------------------------------------------------------------------------------------- 4 㸦㸱㸧ࡑࡢ --------------------------------------------------------------------------------------------------------------------- 4 㸱㸬ᠱ⃮ࠊஙࡢศᩓᛶᑐࡍࡿὀព --------------------------------------------------------------------------------- 4 㸲㸬〇ࡢྛ✀᮲௳ୗ࠾ࡅࡿᏳᐃᛶ ------------------------------------------------------------------------------------ 5 㸳㸬ㄪᩚἲཬࡧ⁐ゎᚋࡢᏳᐃᛶ --------------------------------------------------------------------------------------------- 5 㸴㸬ࡢ㓄ྜኚ㸦≀⌮Ꮫⓗኚ㸧 ------------------------------------------------------------------------------ 5 㸵㸬⁐ฟᛶ ------------------------------------------------------------------------------------------------------------------------ 5 㸶㸬⏕≀Ꮫⓗヨ㦂ἲ ------------------------------------------------------------------------------------------------------------ 5 㸷㸬〇୰ࡢ᭷ຠᡂศࡢ☜ㄆヨ㦂ἲ --------------------------------------------------------------------------------------- 5 㸯㸮㸬〇୰ࡢ᭷ຠᡂศࡢᐃ㔞ἲ ------------------------------------------------------------------------------------------ 5 㸯㸯㸬ຊ౯ ------------------------------------------------------------------------------------------------------------------------ 5 㸯㸰㸬ΰධࡍࡿྍ⬟ᛶࡢ࠶ࡿ∝㞧≀ --------------------------------------------------------------------------------------- 5 㸯㸱㸬ὀពࡀᚲせ࡞ᐜჾ࣭እほࡀ≉Ṧ࡞ᐜჾ㛵ࡍࡿሗ --------------------------------------------------------- 5 㸯㸲㸬ࡑࡢ --------------------------------------------------------------------------------------------------------------------- 5 㹔㸬⒪㛵ࡍࡿ㡯┠ 㸯㸬ຠ⬟ཪࡣຠᯝ --------------------------------------------------------------------------------------------------------------- 6 㸰㸬⏝ἲཬࡧᐜ㔞 --------------------------------------------------------------------------------------------------------------- 6 㸱㸬⮫ᗋᡂ⦼ 㸦㸯㸧⮫ᗋࢹ࣮ࢱࣃࢵࢣ࣮ࢪ ------------------------------------------------------------------------------------------------ 6 㸦㸰㸧⮫ᗋຠᯝ ------------------------------------------------------------------------------------------------------------------ 6 㸦㸱㸧⮫ᗋ⸆⌮ヨ㦂 ------------------------------------------------------------------------------------------------------------ 6 㸦㸲㸧᥈⣴ⓗヨ㦂 --------------------------------------------------------------------------------------------------------------- 6 㸦㸳㸧᳨ドⓗヨ㦂 㸯㸧↓సⅭ୪⾜⏝㔞ᛂヨ㦂 -------------------------------------------------------------------------------------- 6 㸰㸧ẚ㍑ヨ㦂 -------------------------------------------------------------------------------------------------------------- 6 㸱㸧Ᏻᛶヨ㦂 ----------------------------------------------------------------------------------------------------------- 6 㸲㸧ᝈ⪅࣭ែูヨ㦂 -------------------------------------------------------------------------------------------------- 6 㸦㸴㸧⒪ⓗ⏝ 㸯㸧⏝ᡂ⦼ㄪᰝ࣭≉ᐃ⏝ᡂ⦼ㄪᰝ㸦≉ูㄪᰝ㸧 ࣭〇㐀㈍ᚋ⮫ᗋヨ㦂㸦ᕷ㈍ᚋ⮫ᗋヨ㦂㸧------- 6 㸰㸧ᢎㄆ᮲௳ࡋ࡚ᐇணᐃࡢෆᐜཪࡣᐇࡋࡓヨ㦂ࡢᴫせ ----------------------------------------------- 6 㹔,㸬⸆ຠ⸆⌮㛵ࡍࡿ㡯┠ 㸯㸬⸆⌮Ꮫⓗ㛵㐃࠶ࡿྜ≀ཪࡣྜ≀⩌ --------------------------------------------------------------------------- 7 㸰㸬⸆⌮స⏝ 㸦㸯㸧స⏝㒊࣭స⏝ᶵᗎ --------------------------------------------------------------------------------------------------- 7 㸦㸰㸧⸆ຠࢆࡅࡿヨ㦂ᡂ⦼ --------------------------------------------------------------------------------------------- 7 㸦㸱㸧స⏝Ⓨ⌧㛫࣭ᣢ⥆㛫 --------------------------------------------------------------------------------------------- 8 㹔,,㸬⸆≀ືែ㛵ࡍࡿ㡯┠ 㸯㸬⾑୰⃰ᗘࡢ᥎⛣࣭ ᐃἲ 㸦㸯㸧⒪ୖ᭷ຠ࡞⾑୰⃰ᗘ ------------------------------------------------------------------------------------------------ 9 㸦㸰㸧᭱㧗⾑୰⃰ᗘ฿㐩㛫 ------------------------------------------------------------------------------------------------ 9 㸦㸱㸧⮫ᗋヨ㦂࡛☜ㄆࡉࢀࡓ⾑୰⃰ᗘ ------------------------------------------------------------------------------------ 9 㸦㸲㸧୰ẘᇦ --------------------------------------------------------------------------------------------------------------------- 9 㸦㸳㸧㣗࣭ే⏝⸆ࡢᙳ㡪 ------------------------------------------------------------------------------------------------- 10 㸦㸴㸧ẕ㞟ᅋ㸦࣏ࣆ࣮ࣗࣞࢩࣙࣥ㸧ゎᯒࡼࡾุ᫂ࡋࡓ⸆≀యෆືែኚືせᅉ ---------------------------- 10 㸰㸬⸆≀㏿ᗘㄽⓗࣃ࣓࣮ࣛࢱ 㸦㸯㸧ゎᯒ᪉ἲ ---------------------------------------------------------------------------------------------------------------- 10 㸦㸰㸧྾㏿ᗘᐃᩘ ---------------------------------------------------------------------------------------------------------- 10 㸦㸱㸧ࣂ࢜࣋ࣛࣅࣜࢸ ------------------------------------------------------------------------------------------- 10 㸦㸲㸧ᾘኻ㏿ᗘᐃᩘ ---------------------------------------------------------------------------------------------------------- 10 㸦㸳㸧ࢡࣜࣛࣥࢫ ---------------------------------------------------------------------------------------------------------- 10 㸦㸴㸧ศᕸᐜ✚ ---------------------------------------------------------------------------------------------------------------- 10 㸦㸵㸧⾑₢⺮ⓑ⤖ྜ⋡ ------------------------------------------------------------------------------------------------------- 10 㸱㸬྾ ------------------------------------------------------------------------------------------------------------------------- 10 㸲㸬ศᕸ 㸦㸯㸧⾑ᾮ㸫⬻㛵㛛㏻㐣ᛶ ------------------------------------------------------------------------------------------------- 10 㸦㸰㸧⾑ᾮ㸫⫾┙㛵㛛㏻㐣ᛶ ---------------------------------------------------------------------------------------------- 10 㸦㸱㸧ஙỒࡢ⛣⾜ᛶ ------------------------------------------------------------------------------------------------------- 10 㸦㸲㸧㧊ᾮࡢ⛣⾜ᛶ ------------------------------------------------------------------------------------------------------- 10 㸦㸳㸧ࡑࡢࡢ⤌⧊ࡢ⛣⾜ᛶ ------------------------------------------------------------------------------------------- 10 㸳㸬௦ㅰ 㸦㸯㸧௦ㅰ㒊ཬࡧ௦ㅰ⤒㊰ ---------------------------------------------------------------------------------------------- 10 㸦㸰㸧௦ㅰ㛵ࡍࡿ㓝⣲㸦CYP450 ➼㸧ࡢศᏊ✀ ---------------------------------------------------------------- 10 㸦㸱㸧ึᅇ㏻㐣ຠᯝࡢ᭷↓ཬࡧࡑࡢྜ ------------------------------------------------------------------------------- 10 㸦㸲㸧௦ㅰ≀ࡢάᛶࡢ᭷↓ཬࡧẚ⋡ ------------------------------------------------------------------------------------- 11 㸦㸳㸧άᛶ௦ㅰ≀ࡢ㏿ᗘㄽⓗࣃ࣓࣮ࣛࢱ ------------------------------------------------------------------------------- 11 㸴㸬ἥ 㸦㸯㸧ἥ㒊ཬࡧ⤒㊰ ---------------------------------------------------------------------------------------------------- 11 㸦㸰㸧ἥ⋡ ------------------------------------------------------------------------------------------------------------------- 11 㸦㸱㸧ἥ㏿ᗘ ---------------------------------------------------------------------------------------------------------------- 11 㸵㸬ࢺࣛࣥࢫ࣏࣮ࢱ࣮㛵ࡍࡿሗ ------------------------------------------------------------------------------------- 11 㸶㸬㏱ᯒ➼ࡼࡿ㝖ཤ⋡ ---------------------------------------------------------------------------------------------------- 11 㹔,,,㸬Ᏻᛶ㸦⏝ୖࡢὀព➼㸧㛵ࡍࡿ㡯┠ 㸯㸬㆙࿌ෆᐜࡑࡢ⌮⏤ ---------------------------------------------------------------------------------------------------- 12 㸰㸬⚗ᚷෆᐜࡑࡢ⌮⏤㸦ཎ๎⚗ᚷࢆྵࡴ㸧 ------------------------------------------------------------------------- 12 㸱㸬ຠ⬟ཪࡣຠᯝ㛵㐃ࡍࡿ⏝ୖࡢὀពࡑࡢ⌮⏤ ------------------------------------------------------------- 12 㸲㸬⏝ἲཬࡧ⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀពࡑࡢ⌮⏤ ------------------------------------------------------------- 12 㸳㸬ៅ㔜ᢞෆᐜࡑࡢ⌮⏤ ---------------------------------------------------------------------------------------------- 12 㸴㸬㔜せ࡞ᇶᮏⓗὀពࡑࡢ⌮⏤ཬࡧฎ⨨᪉ἲ ---------------------------------------------------------------------- 13 㸵㸬┦స⏝ 㸦㸯㸧ే⏝⚗ᚷࡑࡢ⌮⏤ ------------------------------------------------------------------------------------------------- 13 㸦㸰㸧ే⏝ὀពࡑࡢ⌮⏤ ------------------------------------------------------------------------------------------------- 13 㸶㸬స⏝ 㸦㸯㸧స⏝ࡢᴫせ ---------------------------------------------------------------------------------------------------------- 14 㸦㸰㸧㔜࡞స⏝ึᮇ≧ ------------------------------------------------------------------------------------------- 14 㸦㸱㸧ࡑࡢࡢస⏝ ------------------------------------------------------------------------------------------------------- 15 㸦㸲㸧㡯┠ูస⏝Ⓨ⌧㢖ᗘཬࡧ⮫ᗋ᳨ᰝ್␗ᖖ୍ぴ ------------------------------------------------------------- 15 㸦㸳㸧ᇶ♏ᝈࠊྜేࠊ㔜ᗘཬࡧᡭ⾡ࡢ᭷↓➼⫼ᬒูࡢస⏝Ⓨ⌧㢖ᗘ ------------------------------- 15 㸦㸴㸧⸆≀ࣞࣝࢠ࣮ᑐࡍࡿὀពཬࡧヨ㦂ἲ ---------------------------------------------------------------------- 15 㸷㸬㧗㱋⪅ࡢᢞ ---------------------------------------------------------------------------------------------------------- 15 㸯㸮㸬ዷ፬ࠊ⏘፬ࠊᤵங፬➼ࡢᢞ ---------------------------------------------------------------------------------- 16 㸯㸯㸬ᑠඣ➼ࡢᢞ ------------------------------------------------------------------------------------------------------- 16 㸯㸰㸬⮫ᗋ᳨ᰝ⤖ᯝཬࡰࡍᙳ㡪 ---------------------------------------------------------------------------------------- 16 㸯㸱㸬㐣㔞ᢞ ---------------------------------------------------------------------------------------------------------------- 16 㸯㸲㸬㐺⏝ୖࡢὀព ---------------------------------------------------------------------------------------------------------- 16 㸯㸳㸬ࡑࡢࡢὀព ---------------------------------------------------------------------------------------------------------- 16 㸯㸴㸬ࡑࡢ ------------------------------------------------------------------------------------------------------------------- 16 㹇㹖㸬㠀⮫ᗋヨ㦂㛵ࡍࡿ㡯┠ 㸯㸬⸆⌮ヨ㦂 㸦㸯㸧⸆ຠ⸆⌮ヨ㦂 ---------------------------------------------------------------------------------------------------------- 17 㸦㸰㸧ḟⓗ⸆⌮ヨ㦂 ------------------------------------------------------------------------------------------------------- 17 㸦㸱㸧Ᏻᐃᛶ⸆⌮ヨ㦂 ------------------------------------------------------------------------------------------------------- 17 㸦㸲㸧ࡑࡢࡢ⸆⌮ヨ㦂 ---------------------------------------------------------------------------------------------------- 17 㸰㸬ẘᛶヨ㦂 㸦㸯㸧༢ᅇᢞẘᛶヨ㦂 ---------------------------------------------------------------------------------------------------- 17 㸦㸰㸧ᢞẘᛶヨ㦂 ---------------------------------------------------------------------------------------------------- 17 㸦㸱㸧⏕ṪⓎ⏕ẘᛶヨ㦂 ---------------------------------------------------------------------------------------------------- 17 㸦㸲㸧ࡑࡢࡢ≉Ṧẘᛶ ---------------------------------------------------------------------------------------------------- 17 㹖㸬⟶⌮ⓗ㡯㛵ࡍࡿ㡯┠ 㸯㸬つไ༊ศ ------------------------------------------------------------------------------------------------------------------- 18 㸰㸬᭷ຠᮇ㛫ཪࡣ⏝ᮇ㝈 ------------------------------------------------------------------------------------------------- 18 㸱㸬㈓ἲ࣭ಖᏑ᮲௳ ---------------------------------------------------------------------------------------------------------- 18 㸲㸬⸆ྲྀᢅ࠸ୖࡢὀពⅬ 㸦㸯㸧⸆ᒁ࡛ࡢྲྀࡾᢅ࠸ࡘ࠸࡚ ---------------------------------------------------------------------------------------- 18 㸦㸰㸧⸆ࡢὀព㸦ᝈ⪅➼␃ពࡍࡁᚲ㡲㡯➼㸧 ---------------------------------------------------- 18 㸦㸱㸧ㄪࡢ␃ពⅬࡘ࠸࡚ ------------------------------------------------------------------------------------------- 18 㸳㸬ᢎㄆ᮲௳➼ ---------------------------------------------------------------------------------------------------------------- 18 㸴㸬ໟ ------------------------------------------------------------------------------------------------------------------------- 18 㸵㸬ᐜჾࡢᮦ㉁ ---------------------------------------------------------------------------------------------------------------- 18 㸶㸬ྠ୍ᡂศ࣭ྠຠ⸆ ------------------------------------------------------------------------------------------------------- 18 㸷㸬ᅜ㝿ㄌ⏕ᖺ᭶᪥ ---------------------------------------------------------------------------------------------------------- 18 㸯㸮.〇㐀㈍ᢎㄆᖺ᭶᪥ཬࡧᢎㄆ␒ྕ --------------------------------------------------------------------------------- 18 㸯㸯.⸆౯ᇶ‽㍕ᖺ᭶᪥ --------------------------------------------------------------------------------------------------- 18 㸯㸰㸬ຠ⬟ཪࡣຠᯝ㏣ຍࠊ⏝ἲཬࡧ⏝㔞ኚ᭦࣭㏣ຍ➼ࡢᖺ᭶᪥ཬࡧࡑࡢෆᐜ ------------------------------- 19 㸯㸱㸬ᑂᰝ⤖ᯝࠊホ౯⤖ᯝබ⾲ᖺ᭶᪥ཬࡧࡑࡢෆᐜ ---------------------------------------------------------- 19 㸯㸲㸬ᑂᰝᮇ㛫 ------------------------------------------------------------------------------------------------------------- 19 㸯㸳㸬ᢞᮇ㛫ไ㝈་⸆ရ㛵ࡍࡿሗ ------------------------------------------------------------------------------- 19 㸯㸴㸬ྛ✀ࢥ࣮ࢻ ------------------------------------------------------------------------------------------------------------- 19 㸯㸵㸬ಖ㝤⤥ୖࡢὀព ---------------------------------------------------------------------------------------------------- 19 㹖㹇㸬ᩥ⊩ 㸯㸬ᘬ⏝ᩥ⊩ ------------------------------------------------------------------------------------------------------------------- 20 㸰㸬ࡑࡢࡢཧ⪃ᩥ⊩ ------------------------------------------------------------------------------------------------------- 20 㹖㹇㹇㸬ཧ⪃㈨ᩱ 㸯㸬࡞እᅜ࡛ࡢⓎ≧ἣ ------------------------------------------------------------------------------------------------- 21 㸰㸬ᾏእ࠾ࡅࡿ⮫ᗋᨭሗ ------------------------------------------------------------------------------------------- 21 㹖㹇㹇㹇㸬ഛ⪃ ࡑࡢࡢ㛵㐃㈨ᩱ ------------------------------------------------------------------------------------------------------------- 22 㹇㸬ᴫせ㛵ࡍࡿ㡯┠ 㸯㸬㛤Ⓨࡢ⤒⦋ ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࡣࠊ2009 ᖺ 7 ᭶ 13 ᪥ᑑ〇⸆ᰴᘧ♫࡛〇㐀㈍ ᢎㄆࢆྲྀᚓࡋࠊ2009 ᖺ 11 ᭶ 13 ᪥⸆౯ᇶ‽㍕ࡉࢀࡓ〇ရ࡛࠶ࡿࠋ ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࡣࠊ2000 ᖺ 2 ᭶ 18 ᪥ᑑ〇⸆ᰴᘧ♫࡛〇㐀㈍ ᢎㄆࢆྲྀᚓࡋࠊ2000 ᖺ 7 ᭶ 7 ᪥⸆౯ᇶ‽㍕ࡉࢀࡓ〇ရ࡛࠶ࡿࠋ 㸰㸬〇ရࡢ⒪Ꮫⓗ࣭〇Ꮫ ⓗ≉ᛶ ᡂศ࡛࠶ࡿࢩࣟࢫࢱࢰ࣮ࣝࡣࠊ⾑ᑠᯈจ㞟ᢚไస⏝ᮎᲈ⾑⟶ᣑᙇస⏝ ࢆేࡏᣢࡘ᪂ࡋ࠸ࢱࣉࡢᢠ⾑ᑠᯈ࡛࠶ࡿࠋ 㸦1㸧ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࡣࢩࣟࢫࢱࢰ࣮ࣝ 100mg ࢆྵ᭷ࡍࡿ⥺ධ ࡾࡢ㘄࡛࠶ࡾࠊศᢞࡀྍ⬟࡛࠶ࡿࠋ 㸦2㸧ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࡣࠊGE ༠ࡢ⏦ࡋྜࢃࡏࡼࡾඛⓎရྠ୍ つ᱁ࡢ〇ရࢆࡑࢁ࠼ࡓࡶࡢ࡛࠶ࡿࠋ 㸦3㸧⾑ᑠᯈจ㞟ࢆᢚไࡋࠊඃࢀࡓᢠ⾑ᰦຠᯝࢆ♧ࡍࠋ 㸦4㸧ୗ⫥⾑ὶ㔞ࢆቑຍࡉࡏࠊᮎᲈࡢ⾑⾜ືែࢆᨵၿࡍࡿࠋ 㸦5㸧៏ᛶື⬦㛢ሰᇶ࡙ࡃ₽⒆ࠊ⑊③ࠊ෭ឤ➼ࡢ⾑ᛶㅖ≧ࢆᨵၿ ࡍࡿࠋ 㸦6㸧1 ᪥ 2 ᅇᢞࡼࡾࠊඃࢀࡓ⮫ᗋຠᯝࡀᚓࡽࢀࡿࠋ ,,㸬ྡ⛠㛵ࡍࡿ㡯┠ 㸯.㈍ྡ 㸦㸯㸧ྡ ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࢥ࣮ࢺࣜࢬ࣒㘄 100mg 㸦㸰㸧ὒྡ KORTRYTHM TAB. 50mg KORTRYTHM TAB. 100mg 㸦㸱㸧ྡ⛠ࡢ⏤᮶ ≉࡞ࡋ 㸰㸬୍⯡ྡ 㸦㸯㸧ྡ㸦ྡἲ㸧 ࢩࣟࢫࢱࢰ࣮ࣝ㸦JAN㸧 㸦㸰㸧ὒྡ㸦ྡἲ㸧 Cilostazol㸦JAN㸪INN㸧 㸦㸱㸧ࢫࢸ࣒ ᫂ 㸱㸬ᵓ㐀ᘧཪࡣ♧ᛶᘧ H N O N N N O N 㸲㸬ศᏊᘧཬࡧศᏊ㔞 ศᏊᘧ㸸C20H27N5O2 ศᏊ㔞㸸369.46 㸳㸬Ꮫྡ㸦ྡἲ㸧 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butyloxy]-3,4-dihydroquinolin-2 (1H)-one 㸦IUPAC ྡἲࡼࡿ㸧 㸴㸬័⏝ྡࠊูྡࠊ␎ྕࠊグ ྕ␒ྕ ≉࡞ࡋ 㸵㸬CAS Ⓩ㘓␒ྕ 73963-72-1 ,,,㸬᭷ຠᡂศ㛵ࡍࡿ㡯┠ 㸯㸬≀⌮Ꮫⓗᛶ㉁ 㸦㸯㸧እほ࣭ᛶ≧ ⓑⰍࠥᚤ㯤ⓑⰍࡢ⤖ᬗཪࡣ⤖ᬗᛶࡢ⢊ᮎ࡛࠶ࡿࠋ 㸦㸰㸧⁐ゎᛶ ࣓ࢱࣀ࣮ࣝࠊ࢚ࢱࣀ࣮ࣝ㸦99.5㸧ཪࡣࢭࢺࢽࢺࣜࣝ⁐ࡅࡃࡃࠊỈ ࢇ⁐ࡅ࡞࠸ࠋ 㸦㸱㸧྾‵ᛶ ヱᙜ㈨ᩱ࡞ࡋ ࠊἛⅬࠊ ⼥Ⅼ㸸158㹼162Υ 㸦㸲㸧⼥Ⅼ㸦ศゎⅬ㸧 จᅛⅬ 㸦㸳㸧㓟ሷᇶゎ㞳ᐃᩘ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸴㸧ศ㓄ಀᩘ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸵㸧ࡑࡢࡢ࡞♧ᛶ್ ヱᙜ㈨ᩱ࡞ࡋ 㸰㸬᭷ຠᡂศࡢྛ✀᮲௳ୗ ࠾ࡅࡿᏳᐃᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸱㸬᭷ຠᡂศࡢ☜ㄆヨ㦂ἲ ᪥ᒁࠕࢩࣟࢫࢱࢰ࣮ࣝࠖ☜ㄆヨ㦂ࡼࡿ 㸦1㸧⣸እྍど྾ගᗘ ᐃἲ 㸦2㸧㉥እ྾ࢫ࣌ࢡࢺࣝ ᐃἲ㸦⮯࣒࢝ࣜ࢘㘄ἲ㸧 㸲㸬᭷ຠᡂศࡢᐃ㔞ἲ ᪥ᒁࠕࢩࣟࢫࢱࢰ࣮ࣝࠖᐃ㔞ἲࡼࡿ ᾮయࢡ࣐ࣟࢺࢢࣛࣇ࣮ ሸ㸸࢜ࢡࢱࢹࢩࣝࢩࣜࣝࢩࣜ࢝ࢤࣝ㸦5μm㸧 ⛣ື┦㸸Ỉ࣭ࢭࢺࢽࢺ࣭࣓ࣜࣝࢱࣀ࣮ࣝΰᾮ㸦10㸸7㸸3㸧 ᳨ฟჾ㸸⣸እ྾ගගᗘィ㸦 ᐃἼ㛗㸸254nm㸧 㹇㹔㸬〇㛵ࡍࡿ㡯┠ 㸯㸬ᙧ 㸦㸯㸧ᙧࡢ༊ูࠊእほཬࡧ ᛶ≧ 50mg 㸸 ⓑⰍࠥᚤ㯤Ⰽࡢ⣲㘄 Ⰽ࣭ᙧ ⾲㠃 㠃 ഃ㠃 ┤ᚄ㸦mm㸧 ཌࡉ㸦mm㸧 㔜㔞㸦mg㸧 6.0 2.5 85 እᙧ ࡁࡉ 100mg 㸸 Ⰽ࣭ᙧ ⓑⰍࠥᚤ㯤ⓑⰍࡢ⥺ධࡾ⣲㘄 ⾲㠃 㠃 ഃ㠃 ┤ᚄ㸦mm㸧 ཌࡉ㸦mm㸧 㔜㔞㸦mg㸧 8.0 3.0 170 እᙧ ࡁࡉ 㸦㸰㸧〇ࡢ≀ᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧㆑ูࢥ࣮ࢻ 50mg 㸸KTB 46 100mg 㸸KTB 45 㸦㸲㸧pHࠊᾐ㏱ᅽẚࠊ⢓ᗘࠊ ヱᙜ㈨ᩱ࡞ࡋ ẚ㔜ࠊ↓⳦ࡢ᪨ཬࡧᏳ ᐃ࡞ pH ᇦ➼ 㸰㸬〇ࡢ⤌ᡂ 㸦㸯㸧᭷ຠᡂศ㸦άᛶᡂศ㸧 ࡢྵ㔞 50mg 㸸1 㘄୰᪥ᒁࢩࣟࢫࢱࢰ࣮ࣝ 50mg 100mg 㸸1 㘄୰᪥ᒁࢩࣟࢫࢱࢰ࣮ࣝ 100mg 㸦㸰㸧ῧຍ≀ ⤖ᬗࢭ࣮ࣝࣟࢫࠊங⢾Ỉ≀ࠊࢺ࢘ࣔࣟࢥࢩࢹࣥࣉࣥࠊ࣐ࢡࣟࢦ࣮ࣝࠊࢡ ࣟࢫ࣓࣮࢝ࣝࣟࢫ Naࠊ࣓ࢳࣝࢭ࣮ࣝࣟࢫࠊࢫࢸࣜࣥ㓟 Mg 㸦㸱㸧ࡑࡢ ≉࡞ࡋ 㸱㸬ᠱ⃮ࠊஙࡢศᩓᛶ ᑐࡍࡿὀព ヱᙜࡋ࡞࠸ 㸲㸬〇ࡢྛ✀᮲௳ୗ࠾ࡅ ࡿᏳᐃᛶ㸵㸧 50mg㸸᭱⤊ໟ〇ရࢆ⏝࠸ࡓຍ㏿ヨ㦂㸦40Υࠊ┦ᑐ‵ᗘ 75㸣ࠊ6 ࣧ᭶㸧 ࡢ⤖ᯝࠊࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࡣ㏻ᖖࡢᕷሙὶ㏻ୗ࠾࠸࡚ 3 ᖺ 㛫Ᏻᐃ࡛࠶ࡿࡇࡀ᥎ ࡉࢀࡓࠋ 100mg㸸᭱⤊ໟ〇ရࢆ⏝࠸ࡓ㛗ᮇಖᏑヨ㦂㸦࡞ࡾࡺࡁ ᗘཬࡧ‵ᗘࠊ3 ᖺ㛫㸧ࡢ⤖ᯝࠊእほཬࡧྵ㔞➼ࡣつ᱁ࡢ⠊ᅖෆ࡛࠶ࡾࠊࢥ࣮ࢺࣜ ࢬ࣒㘄 100mg ࡣ㏻ᖖࡢᕷሙὶ㏻ୗ࠾࠸࡚ 3 ᖺ㛫Ᏻᐃ࡛࠶ࡿࡇ ࡀ☜ㄆࡉࢀࡓࠋ ಖᏑᙧែ ಖᏑ᮲௳ ಖᏑᮇ㛫 ⤖ ᯝ PTP ໟရࠊ⣬⟽ධࡾ 40Υࠊ75㸣RH 6 ࣨ᭶ ኚ࡞ࡋ 㸳㸬ㄪᩚἲཬࡧ⁐ゎᚋࡢᏳᐃᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸴㸬ࡢ㓄ྜኚ㸦≀⌮ Ꮫⓗኚ㸧 ヱᙜ㈨ᩱ࡞ࡋ 㸵㸬⁐ฟᛶ㸱㸧㸲㸧 ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ཬࡧࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࡣࠊ᪥ᮏ⸆ᒁ᪉་⸆ရ ྛ᮲ᐃࡵࡽࢀࡓࢩࣟࢫࢱࢰ࣮ࣝ㘄ࡢ⁐ฟつ᱁㐺ྜࡋ࡚࠸ࡿࡇࡀ☜ ㄆࡉࢀ࡚࠸ࡿࠋ 㸶㸬⏕≀Ꮫⓗヨ㦂ἲ ヱᙜࡋ࡞࠸ 㸷㸬〇୰ࡢ᭷ຠᡂศࡢ☜ㄆ ヨ㦂ἲ ᪥ᒁࠕࢩࣟࢫࢱࢰ࣮ࣝࠖ☜ㄆヨ㦂ࡼࡿ ⷧᒙࢡ࣐ࣟࢺࢢࣛࣇ࣮ 㸯㸮㸬〇୰ࡢ᭷ຠᡂศࡢᐃ 㔞ἲ ᪥ᒁࠕࢩࣟࢫࢱࢰ࣮ࣝࠖᐃ㔞ἲࡼࡿ ᾮయࢡ࣐ࣟࢺࢢࣛࣇ࣮ ሸ㸸࢜ࢡࢱࢹࢩࣝࢩࣜࣝࢩࣜ࢝ࢤࣝ㸦5μm㸧 ⛣ື┦㸸Ỉ࣭ࢭࢺࢽࢺ࣭࣓ࣜࣝࢱࣀ࣮ࣝΰᾮ㸦10㸸7㸸3㸧 ᳨ฟჾ㸸⣸እ྾ගගᗘィ㸦 ᐃἼ㛗㸸254nm㸧 㸯㸯㸬ຊ౯ ヱᙜࡋ࡞࠸ 㸯㸰㸬ΰධࡍࡿྍ⬟ᛶࡢ࠶ࡿ ዃ㞧≀ ヱᙜ㈨ᩱ࡞ࡋ 㸯㸱㸬ὀពࡀᚲせ࡞ᐜჾ࣭እ ほࡀ≉Ṧ࡞ᐜჾ㛵ࡍ ࡿሗ ヱᙜ㈨ᩱ࡞ࡋ 㸯㸲㸬ࡑࡢ ≉࡞ࡋ 㹔㸬⒪㛵ࡍࡿ㡯┠ 㸯㸬ຠ⬟ཪࡣຠᯝ ࣭៏ᛶື⬦㛢ሰᇶ࡙ࡃ₽⒆ࠊ⑊③ཬࡧ෭ឤ➼ࡢ⾑ᛶㅖ≧ࡢᨵၿ ࣭⬻᱾ሰ㸦ᚰཎᛶ⬻ሰᰦࢆ㝖ࡃ㸧ⓎᚋࡢⓎᢚไ 㸰㸬⏝ἲཬࡧ⏝㔞 ㏻ᖖࠊᡂேࡣࠊࢩࣟࢫࢱࢰ࣮ࣝࡋ࡚ 1 ᅇ 100mg ࢆ 1 ᪥ 2 ᅇ⤒ཱྀᢞ ࡍࡿࠋ࡞࠾ࠊᖺ㱋࣭≧ࡼࡾ㐺ᐅቑῶࡍࡿࠋ 㸱㸬⮫ᗋᡂ⦼ 㸦㸯㸧⮫ᗋࢹ࣮ࢱࣃࢵࢣ࣮ࢪ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸰㸧⮫ᗋຠᯝ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧⮫ᗋ⸆⌮ヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸲㸧᥈⣴ⓗヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸳㸧᳨ドⓗヨ㦂 㸯㸧↓సⅭ୪⾜⏝㔞 ᛂヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸰㸧ẚ㍑ヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸱㸧Ᏻᛶヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸲㸧ᝈ⪅㺃ែูヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸴㸧⒪ⓗ⏝ 㸯㸧⏝ᡂ⦼ㄪᰝ࣭≉ᐃ ⏝ᡂ⦼ㄪᰝ㸦≉ู ㄪᰝ㸧 ࣭〇㐀㈍ᚋ⮫ ᗋヨ㦂㸦ᕷ㈍ᚋ⮫ᗋ ヨ㦂㸧 㸰㸧ᢎㄆ᮲௳ࡋ࡚ᐇ ணᐃࡢෆᐜཪࡣᐇ ࡋࡓヨ㦂ࡢᴫせ ヱᙜ㈨ᩱ࡞ࡋ ヱᙜ㈨ᩱ࡞ࡋ 㹔,㸬⸆ຠ⸆⌮㛵ࡍࡿ㡯┠ 㸯㸬⸆⌮Ꮫⓗ㛵㐃࠶ࡿྜ ≀ཪࡣྜ≀⩌ 㸰㸬⸆⌮స⏝ 㸦㸯㸧స⏝㒊࣭స⏝ᶵᗎ 㸦㸰㸧⸆ຠࢆࡅࡿヨ㦂ᡂ⦼ 㸦1㸧ᢠ⾑ᑠᯈ ࢫࣆࣜࣥࠊࢪࣆࣜࢲ࣮ࣔࣝࠊࢫࣝࣇࣥࣆࣛࢰࣥࠊࢳࢡࣟࣆࢪࣥሷ 㓟ሷࠊࢥࢧ࣌ࣥࢱ࢚ࣥ㓟࢚ࢳࣝࠊ࣋ࣛࣉࣟࢫࢺࢼࢺ࣒ࣜ࢘ࠊࢧ࣏ࣝ ࢢ࣮ࣞࣛࢺሷ㓟ሷ ➼ 㸦2㸧ᮎᲈ⾑⟶ᣑᙇ ࣐ࣜࣉࣟࢫࢺࠊࣝࣉࣟࢫࢱࢪࣝࠊࢺࢥࣇ࢙࣮ࣟࣝࢽࢥࢳࣥ㓟࢚ࢫࢸ ࣝࠊ࢝ࣜࢪࣀࢤࢼ࣮ࢮࠊࢪࣄࢻ࢚ࣟࣝࢦࢺ࢟ࢩ࣓ࣥࢩࣝ㓟ሷࠊࢺࣛࣆ ࢪࣝࠊࢪࣛࢮࣉሷ㓟ሷࠊࣃࣃ࣋ࣜࣥሷ㓟ሷ ➼ 㸦1㸧࣍ࢫ࣍ࢪ࢚ࢫࢸ࣮ࣛࢮ 3㸦PDE3㸧άᛶࢆ㜼ᐖࡍࡿࡇࡼࡾࠊcAMP ⃰ᗘࢆୖ᪼ࡉࡏࠊ⾑ᑠᯈจ㞟ࢆᢚไࡍࡿࠋ 㸦2㸧⾑⟶ᖹ➽⣽⬊ෆࡢ cAMP ⃰ᗘࢆୖ᪼ࡉࡏࠊ⾑⟶ࢆᣑᙇࡉࡏࡿࠋ ᢠ⾑ᑠᯈస⏝ 㸦1㸧ᢠ ࣄࢺ⾑ᑠᯈ࠾࠸࡚ࠊADPࠊࢥ࣮ࣛࢤࣥࠊࣛ࢟ࢻࣥ㓟ࠊࢻࣞࢼࣜ ࣥࡼࡿ⾑ᑠᯈจ㞟ࢆᢚไࡍࡿ㸦in vitro㸧㸳㸧ࠋ Q 0HDQs6( 㻭㻰㻼 䝁䝷䞊䝀䞁 ȣ0 㸦 㻝㻜㻜 ȣJPO 㸦 㻝㻜㻜 䝅䝻䝇䝍䝌䞊䝹 㻤㻜 㻤㻜 ⾑ ᑠ ᯈ 㻢㻜 จ 㞟 㻠㻜 ᢚ ไ 㻞㻜 ⋡ ⾑ ᑠ ᯈ 㻢㻜 จ 㞟 㻠㻜 ᢚ ไ 㻞㻜 ⋡ 䜰䝇䝢䝸䞁 㻜 䝅䝻䝇䝍䝌䞊䝹 㻜 㻝 㻝㻜 㻝㻜㻜 㻝㻜㻜㻜 㸦ȣ0 㻜㻚㻝 㻝 ⸆≀⃰ᗘ 䝅䝻䝇䝍䝌䞊䝹 㻝㻜㻜 㻝㻜㻜㻜 㸦ȣ0 䜰䝷䜻䝗䞁㓟 ȣJPO ȣJPO 㸦 㻝㻜㻜 㻤㻜 䝅䝻䝇䝍䝌䞊䝹 㻤㻜 ⾑ ᑠ ᯈ 㻢㻜 จ 㞟 㻠㻜 ᢚ ไ 㻞㻜 ⋡ 㻝㻜 ⸆≀⃰ᗘ 䜶䝢䝛䝣䝸䞁 㸦 㻝㻜㻜 䜰䝇䝢䝸䞁 ⾑ ᑠ ᯈ 㻢㻜 จ 㞟 㻠㻜 ᢚ ไ 㻞㻜 ⋡ 䜰䝇䝢䝸䞁 㻜 䜰䝇䝢䝸䞁 㻜 㻝 㻝㻜 㻝㻜㻜 ⸆≀⃰ᗘ 㻝㻜㻜㻜 㸦ȣ0 㻜㻚㻝 㻝 㻝㻜 㻝㻜㻜 ⸆≀⃰ᗘ 㻝㻜㻜㻜 㸦ȣ0 㸦2㸧ᢠ ᢠ⾑ᰦస⏝ ࣐࢘ࢫ࠾࠸࡚ࠊADPࠊࢥ࣮ࣛࢤࣥࢆ㟼⬦ෆᢞࡍࡿࡇࡼࡾㄏⓎ ࡉࢀࡿ⫵ሰᰦ⮴Ṛࢆᢚไࡍࡿ㸴㸧ࠋ Q 3 3 㻭㻰㻼ㄏᑟ 㻔㻑㻕 䝁䝷䞊䝀䞁ㄏᑟ 㻔㻑㻕 䠆䠆 䠆䠆 䠆 Ṛ ஸ ᢚ ไ ⋡ Ṛ ஸ ᢚ ไ ⋡ 䠆 䠆 䝅䝻䝇䝍䝌䞊䝹 㻔㼙㼓㻛㼗㼓㻕 䝏䜽䝻䝢䝆䞁 ⸆ཬ䜃ᢞ㔞 㸦㸱㸧స⏝Ⓨ⌧㛫࣭ᣢ⥆㛫 ヱᙜ㈨ᩱ࡞ࡋ 䝅䝻䝇䝍䝌䞊䝹 䝏䜽䝻䝢䝆䞁 ⸆ཬ䜃ᢞ㔞 㻔㼙㼓㻛㼗㼓㻕 㹔,,㸬⸆≀ືែ㛵ࡍࡿ㡯┠ 㸯㸬⾑୰⃰ᗘࡢ᥎⛣࣭ ᐃἲ 㸦㸯㸧⒪ୖ᭷ຠ࡞⾑୰⃰ᗘ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸰㸧᭱㧗⾑୰⃰ᗘ฿㐩㛫 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧⮫ᗋヨ㦂࡛☜ㄆࡉࢀࡓ ⾑୰⃰ᗘ 㸺⏕≀Ꮫⓗྠ➼ᛶヨ㦂㸼 ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ᶆ‽〇ࢆࠊ ࢡࣟࢫ࣮࢜ࣂ࣮ἲࡼࡾࡑࢀࡒࢀ 1 㘄㸦ࢩࣟࢫࢱࢰ࣮ࣝ 100mg㸧ᗣᡂே⏨Ꮚ⤯㣗༢ᅇ⤒ཱྀᢞࡋ࡚⾑₢୰ ᮍኚయ⃰ᗘࢆ ᐃࡋࠊᚓࡽࢀࡓ⸆≀ືែࣃ࣓࣮ࣛࢱ㸦AUCtࠊCmax㸧 ࡘ࠸࡚⤫ィゎᯒࢆ⾜ࡗࡓ⤖ᯝࠊ୧ࡢ⏕≀Ꮫⓗྠ➼ᛶࡀ☜ㄆࡉࢀࡓ㸯㸧ࠋ ࢥ࣮ࢺࣜࢬ࣒ 㘄 100mg ᶆ‽〇 (㘄ࠊ100mg) AUCt (ng㺃hr/mL) Cmax (ng/mL) Tmax (hr) T1/2 (hr) 9431.0±2351.5 880.9±238.8 3.0±1.2 20.8±11.5 9714.0±2461.0 812.1±202.8 3.0±0.7 25.4±23.2 㸦MeansS.D., n=20㸧 㻔㼚㼓㻛㼙㻸㻕 㻝㻞㻜㻜 ⾑ ₢ 㻝㻜㻜㻜 ୰ 䝅 㻤㻜㻜 䝻 䝇 㻢㻜㻜 䝍 䝌 呎 㻠㻜㻜 䝹 ⃰ 㻞㻜㻜 ᗘ 䝁䞊䝖䝸䝈䝮㘄㻝㻜㻜㼙㼓 ᶆ‽ရ 㻹㼑㼍㼚㼼㻿㻚㻰㻚㻘㻌㼚䠙㻞㻜 㻜 㻜 㻝㻞 㻞㻠 㻟㻢 㻠㻤 㻢㻜 㛫㻌㻔㼔㼞㻕 ⾑₢୰⃰ᗘ୪ࡧ AUCtࠊCmax ➼ࡢࣃ࣓࣮ࣛࢱࡣࠊ⿕㦂⪅ࡢ㑅ᢥࠊయᾮ ࡢ᥇ྲྀᅇᩘ࣭㛫➼ࡢヨ㦂᮲௳ࡼࡗ࡚␗࡞ࡿྍ⬟ᛶࡀ࠶ࡿࠋ ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࡣࠕྵ㔞ࡀ␗࡞ࡿ⤒ཱྀᅛᙧ〇ࡢ⏕≀Ꮫⓗྠ➼ᛶヨ 㦂࢞ࢻࣛࣥ㸦ᖹᡂ 18 ᖺ 11 ᭶ 24 ᪥⸆㣗ᑂ 1124004 ྕ㸧ࠖᇶ࡙ࡁࠊ ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࢆᶆ‽〇ࡋࡓࡁࠊ⁐ฟᣲືࡀ➼ࡋࡃࠊ⏕≀ Ꮫⓗྠ➼ࡳ࡞ࡉࢀࡓ㸰㸧ࠋ 㸦㸲㸧୰ẘᇦ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸳㸧㣗࣭ే⏝⸆ࡢᙳ㡪 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸴㸧ẕ㞟ᅋ㸦࣏ࣆ࣮ࣗࣞࢩ ࣙࣥ㸧ゎᯒࡼࡾุ᫂ ࡋࡓ⸆≀యෆືែኚື せᅉ ヱᙜ㈨ᩱ࡞ࡋ 㸰㸬⸆≀㏿ᗘㄽⓗࣃ࣓࣮ࣛࢱ 㸦㸯㸧ゎᯒ᪉ἲ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸰㸧྾㏿ᗘᐃᩘ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧ࣂ࢜࣋ࣛࣅࣜࢸ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸲㸧ᾘኻ㏿ᗘᐃᩘ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸳㸧ࢡࣜࣛࣥࢫ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸴㸧ศᕸᐜ✚ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸵㸧⾑₢⺮ⓑ⤖ྜ⋡ ヱᙜ㈨ᩱ࡞ࡋ 㸱㸬྾ ヱᙜ㈨ᩱ࡞ࡋ 㸲㸬ศᕸ 㸦㸯㸧⾑ᾮ㸫⬻㛵㛛㏻㐣ᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸰㸧⾑ᾮ㸫⫾┙㛵㛛㏻㐣ᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧ஙỒࡢ⛣⾜ᛶ 㸦 ࠕ㹔㹇㹇㹇㸬Ᏻᐃᛶ㸦⏝ୖࡢὀព➼㸧㛵ࡍࡿ㡯┠ 㸯㸮㸬ዷ፬ࠊ⏘ ፬ࠊᤵங፬➼ࡢᢞࠖࡢ㡯ཧ↷㸧 㸦㸲㸧㧊ᾮࡢ⛣⾜ᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸳㸧ࡑࡢࡢ⤌⧊ࡢ⛣⾜ᛶ ヱᙜ㈨ᩱ࡞ࡋ 㸳㸬௦ㅰ 㸦㸯㸧௦ㅰ㒊ཬࡧ௦ㅰ⤒㊰ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸰㸧௦ㅰ㛵ࡍࡿ㓝⣲ 㸦CYP450 ➼㸧ࡢศᏊ✀ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧ึᅇ㏻㐣ຠᯝࡢ᭷↓ཬ ࡧࡑࡢྜ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸲㸧௦ㅰ≀ࡢάᛶࡢ᭷↓ཬ ࡧẚ⋡ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸳㸧άᛶ௦ㅰ≀ࡢ㏿ᗘㄽⓗ ࣃ࣓࣮ࣛࢱ ヱᙜ㈨ᩱ࡞ࡋ 㸴㸬ἥ 㸦㸯㸧ἥ㒊ཬࡧ⤒㊰ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸰㸧ἥ⋡ ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧ἥ㏿ᗘ ヱᙜ㈨ᩱ࡞ࡋ 㸵㸬ࢺࣛࣥࢫ࣏࣮ࢱ࣮㛵ࡍ ࡿሗ ヱᙜ㈨ᩱ࡞ࡋ 㸶㸬㏱ᯒ➼ࡼࡿ㝖ཤ⋡ ヱᙜ㈨ᩱ࡞ࡋ 㹔,,,㸬Ᏻᛶ㸦⏝ୖࡢὀព➼㸧㛵ࡍࡿ㡯┠ 㸯㸬㆙࿌ෆᐜࡑࡢ⌮⏤ ᮏࡢᢞࡼࡾ⬦ᢿᩘࡀቑຍࡋࠊ⊃ᚰࡀⓎ⌧ࡍࡿࡇࡀ࠶ࡿࡢ࡛ࠊ⊃ ᚰࡢ≧㸦⬚③➼㸧ᑐࡍࡿၥデࢆὀព῝ࡃ⾜࠺ࡇࠋࠝ⬻᱾ሰⓎᢚ ไ ຠ ᯝ ࢆ ᳨ ウ ࡍ ࡿ ヨ 㦂 ࠾ ࠸ ࡚ ࠊ 㛗 ᮇ ࢃ ࡓ ࡾ PRP 㸦 pressure rateproduct㸧ࢆ᭷ពୖ᪼ࡉࡏࡿస⏝ࡀㄆࡵࡽࢀࡓࠋࡲࡓࠊᮏᢞ⩌ ⊃ᚰࢆⓎ⌧ࡋࡓࡀࡳࡽࢀࡓࠋࠞ㸦ࠕៅ㔜ᢞ㸦4㸧ࠖࡢ㡯ࠊࠕ㔜 せ࡞ᇶᮏⓗὀព㸦3㸧ࠖࡢ㡯ࠊࠕ㔜࡞స⏝ 1㸧ࠖࡢ㡯ཧ↷㸧 㸰㸬⚗ᚷෆᐜࡑࡢ⌮⏤㸦ཎ ๎⚗ᚷࢆྵࡴ㸧 㸦1㸧ฟ⾑ࡋ࡚࠸ࡿᝈ⪅㸦⾑ࠊẟ⣽⾑⟶⬤ᙅࠊ㢌ෆฟ⾑ࠊᾘ⟶ ฟ⾑ࠊᒀ㊰ฟ⾑ࠊၻ⾑ࠊ◪Ꮚయฟ⾑➼㸧ࠝฟ⾑ࢆຓ㛗ࡍࡿ࠾ࡑࢀࡀ࠶ ࡿࠋࠞ 㸦2㸧࠺ࡗ⾑ᛶᚰࡢᝈ⪅ࠝ≧ࢆᝏࡉࡏࡿ࠾ࡑࢀࡀ࠶ࡿࠋࠞ㸦ࠕ㔜 せ࡞ᇶᮏⓗὀព㸦4㸧ࠖࡢ㡯ཧ↷㸧 㸦3㸧ᮏࡢᡂศᑐࡋ㐣ᩄࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅ 㸦4㸧ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿ፬ே㸦ࠕዷ፬ࠊ⏘፬ࠊᤵங፬➼ ࡢᢞࠖࡢ㡯ཧ↷㸧 㸱㸬ຠ⬟ཪࡣຠᯝ㛵㐃ࡍࡿ ⏝ୖࡢὀពࡑࡢ⌮⏤ ↓ೃᛶ⬻᱾ሰ࠾ࡅࡿᮏࡢ⬻᱾ሰⓎసࡢᢚไຠᯝࡣ᳨ウࡉࢀ࡚࠸࡞ ࠸ࠋ 㸲㸬⏝ἲཬࡧ⏝㔞㛵㐃ࡍࡿ ⏝ୖࡢὀពࡑࡢ⌮⏤ ヱᙜࡋ࡞࠸ 㸳㸬ៅ㔜ᢞෆᐜࡑࡢ⌮⏤ 㸦1㸧ᢠจᅛ㸦࣡ࣝࣇࣜࣥ➼㸧ࠊ⾑ᑠᯈจ㞟ࢆᢚไࡍࡿ⸆㸦ࢫࣆࣜ ࣥࠊࢳࢡࣟࣆࢪࣥሷ㓟ሷࠊࢡࣟࣆࢻࢢࣞࣝ◲㓟ሷ➼㸧 ࠊ⾑ᰦ⁐ゎ㸦࢘ ࣟ࢟ࢼ࣮ࢮࠊࣝࢸࣉ࣮ࣛࢮ➼㸧ࠊࣉࣟࢫࢱࢢࣛࣥࢪࣥE1〇ཬࡧࡑ ࡢㄏᑟయ㸦ࣝࣉࣟࢫࢱࢪࣝࠊ࣐ࣜࣉࣟࢫࢺࣝࣇࢹࢡࢫ➼㸧ࢆᢞ ୰ࡢᝈ⪅㸦 ࠕ┦స⏝ࠖࡢ㡯ཧ↷㸧 㸦2㸧᭶⤒ᮇ㛫୰ࡢᝈ⪅ࠝฟ⾑ࢆຓ㛗ࡍࡿ࠾ࡑࢀࡀ࠶ࡿࠋ ࠞ 㸦3㸧ฟ⾑ഴྥ୪ࡧࡑࡢ⣲ᅉࡢ࠶ࡿᝈ⪅ࠝฟ⾑ࡋࡓࠊࡑࢀࢆຓ㛗ࡍࡿ ࠾ࡑࢀࡀ࠶ࡿࠋ ࠞ 㸦4㸧ෙື⬦⊃✽ࢆྜేࡍࡿᝈ⪅ࠝᮏᢞࡼࡿ⬦ᢿᩘቑຍࡼࡾ⊃ᚰ ࢆㄏⓎࡍࡿྍ⬟ᛶࡀ࠶ࡿࠋࠞ 㸦ࠕ㔜せ࡞ᇶᮏⓗὀព㸦3㸧 ࠖࡢ㡯ࠊ ࠕ㔜 ࡞స⏝ 1㸧 ࠖࡢ㡯ཧ↷㸧 㸦5㸧⢾ᒀ࠶ࡿ࠸ࡣ⪏⢾⬟␗ᖖࢆ᭷ࡍࡿᝈ⪅ࠝฟ⾑ᛶ᭷ᐖ㇟ࡀⓎ⌧ࡋ ࡸࡍ࠸ࠋ ࠞ 㸦6㸧㔜⠜࡞⫢㞀ᐖࡢ࠶ࡿᝈ⪅ࠝࢩࣟࢫࢱࢰ࣮ࣝࡢ⾑୰⃰ᗘࡀୖ᪼ࡍࡿ࠾ ࡑࢀࡀ࠶ࡿࠋ ࠞ 㸦7㸧⭈㞀ᐖࡢ࠶ࡿᝈ⪅ࠝ⭈ᶵ⬟ࡀᝏࡍࡿ࠾ࡑࢀࡀ࠶ࡿࠋࡲࡓࠊࢩࣟࢫ ࢱࢰ࣮ࣝࡢ௦ㅰ≀ࡢ⾑୰⃰ᗘࡀୖ᪼ࡍࡿ࠾ࡑࢀࡀ࠶ࡿࠋ 㸦ࠕ㔜࡞స ⏝ 7㸧 ࠖࡢ㡯ཧ↷㸧 㸦8㸧ᣢ⥆ࡋ࡚⾑ᅽࡀୖ᪼ࡋ࡚࠸ࡿ㧗⾑ᅽࡢᝈ⪅㸦ᝏᛶ㧗⾑ᅽ➼㸧㸦 ࠕࡑࡢ ࡢὀព㸦2㸧ࠖࡢ㡯ཧ↷㸧 㸴㸬㔜せ࡞ᇶᮏⓗὀពࡑࡢ ⌮⏤ཬࡧฎ⨨᪉ἲ 㸦1㸧ᮏࡢ⬻᱾ሰᝈ⪅ᑐࡍࡿᢞࡣ⬻᱾ሰࡢ≧ࡀᏳᐃࡋ࡚ࡽ㛤ጞ ࡍࡿࡇࠋ 㸦2㸧⬻᱾ሰᝈ⪅ࡢᢞ࠶ࡓࡗ࡚ࡣࠊࡢ⾑ᑠᯈจ㞟ࢆᢚไࡍࡿ⸆ ➼ࡢ┦స⏝ὀពࡍࡿࡶࠊ㧗⾑ᅽࡀᣢ⥆ࡍࡿᝈ⪅ࡢᢞ ࡣៅ㔜⾜࠸ࠊᢞ୰ࡣ༑ศ࡞⾑ᅽࡢࢥࣥࢺ࣮ࣟࣝࢆ⾜࠺ࡇࠋ㸦ࠕ┦ స⏝ࠖࡢ㡯ཧ↷㸧 㸦3㸧ෙື⬦⊃✽ࢆྜేࡍࡿᝈ⪅࡛ࠊᮏࢆᢞ୰㐣ᗘࡢ⬦ᢿᩘቑຍࡀ ࠶ࡽࢃࢀࡓሙྜࡣࠊ⊃ᚰࢆㄏⓎࡍࡿྍ⬟ᛶࡀ࠶ࡿࡢ࡛ࠊࡇࡢࡼ࠺ ࡞ሙྜࡣῶ㔞ཪࡣ୰Ṇࡍࡿ࡞ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ㸦ࠕ㆙࿌ࠖ ࡢ㡯ࠊࠕៅ㔜ᢞ㸦4㸧ࠖࡢ㡯ࠊࠕ㔜࡞స⏝ 1㸧ࠖࡢ㡯ཧ↷㸧 㸦4㸧ᮏࡣPDE3㜼ᐖస⏝ࢆ᭷ࡍࡿ⸆࡛࠶ࡿࠋᾏእ࠾࠸࡚PDE3㜼ᐖ స⏝ࢆ᭷ࡍࡿ⸆㸦࣑ࣝࣜࣀࣥࠊ࣋ࢫࢼࣜࣀࣥ㸧㛵ࡋ࡚ࡣࠊ࠺ࡗ⾑ ᛶᚰ㸦NYHAศ㢮Ϫࠥϫ㸧ᝈ⪅ࢆᑐ㇟ࡋࡓࣉࣛࢭ࣎ᑐ↷㛗ᮇẚ ㍑ヨ㦂࠾࠸࡚ࠊ⏕Ꮡ⋡ࡀࣉࣛࢭ࣎ࡼࡾపࡗࡓࡢሗ࿌ࡀ࠶ࡿࠋࡲ ࡓࠊ࠺ࡗ⾑ᛶᚰࢆ᭷ࡋ࡞࠸ᝈ⪅࠾࠸࡚ࠊᮏࢆྵࡴPDE3㜼ᐖ ࢆ㛗ᮇᢞࡋࡓሙྜࡢணᚋࡣ᫂ࡽ࡛ࡣ࡞࠸ࠋ 㸵㸬┦స⏝ ᮏࡣࠊࡋ࡚⫢௦ㅰ㓝⣲CYP3A4ཬࡧ୍㒊CYP2D6ࠊCYP2C19࡛௦ ㅰࡉࢀࡿࠋ 㸦㸯㸧ే⏝⚗ᚷࡑࡢ⌮⏤ ヱᙜࡋ࡞࠸ 㸦㸰㸧ే⏝ὀពࡑࡢ⌮⏤ ⸆ྡ➼ ⮫ᗋ≧࣭ᥐ⨨᪉ἲ ᶵᗎ࣭༴㝤ᅉᏊ ᢠจᅛ ࣡ࣝࣇࣜࣥ➼ ⾑ᑠᯈจ㞟ࢆᢚไࡍ ࡿ⸆ ࢫࣆࣜࣥࠊࢳࢡࣟ ࣆࢪࣥሷ㓟ሷࠊࢡࣟ ࣆࢻࢢࣞࣝ◲㓟ሷ ➼ ⾑ᰦ⁐ゎ ࢘ࣟ࢟ࢼ࣮ࢮࠊࣝ ࢸࣉ࣮ࣛࢮ➼ ࣉࣟࢫࢱࢢࣛࣥࢪࣥ E1〇ཬࡧࡑࡢㄏᑟ య ࣝࣉࣟࢫࢱࢪࣝࠊ ࣐ࣜࣉࣟࢫࢺ ࣝࣇࢹࢡࢫ➼ ฟ⾑ࡋࡓࠊࡑࢀࢆຓ 㛗ࡍࡿ࠾ࡑࢀࡀ࠶ࡿࠋ ే⏝ࡣฟ⾑➼ࡢ స⏝ࢆண▱ࡍࡿࡓ ࡵࠊ⾑ᾮจᅛ⬟᳨ᰝ➼ ࢆ༑ศ⾜࠺ࠋ ᮏࡣ⾑ᑠᯈจ㞟ᢚ ไస⏝ࢆ᭷ࡍࡿࡓࡵࠊ ࡇࢀࡽ⸆ే⏝ࡍ ࡿฟ⾑ࢆຓ㛗ࡍࡿ ࠾ࡑࢀࡀ࠶ࡿࠋ ⸆ྡ➼ ⮫ᗋ≧࣭ᥐ⨨᪉ἲ ᶵᗎ࣭༴㝤ᅉᏊ ⸆ ≀ ௦ ㅰ 㓝 ⣲ 㸦CYP3A4㸧ࢆ㜼ᐖࡍ ࡿ⸆ ࣐ࢡࣟࣛࢻ⣔ᢠ ⏕≀㉁㸦࢚ࣜࢫ࣐ࣟ ࢩࣥ➼㸧 HIV ࣉࣟࢸ࣮ࢮ 㜼ᐖ㸦ࣜࢺࢼࣅࣝ ➼㸧ࢰ࣮ࣝ⣔ᢠ┿ ⳦㸦ࢺࣛࢥࢼࢰ ࣮ࣝࠊ࣑ࢥࢼࢰ࣮ࣝ ➼㸧 ࢩ࣓ࢳࢪࣥࠊࢪࣝࢳ ࢮ࣒ሷ㓟ሷ➼ ࢢ࣮ࣞࣉࣇ࣮ࣝࢶ ࢪ࣮ࣗࢫ ᮏࡢస⏝ࡀቑᙉࡍ ࡿ࠾ࡑࢀࡀ࠶ࡿࠋే⏝ ࡍࡿሙྜࡣῶ㔞࠶ࡿ ࠸ࡣప⏝㔞ࡽ㛤ጞ ࡍࡿ࡞ὀពࡍࡿࡇ ࠋ ࡲࡓࠊࢢ࣮ࣞࣉࣇ࣮ࣝ ࢶࢪ࣮ࣗࢫࡢྠ ᭹⏝ࢆࡋ࡞࠸ࡼ࠺ ὀពࡍࡿࡇࠋ ࡇࢀࡽࡢ⸆࠶ࡿ࠸ ࡣࢢ࣮ࣞࣉࣇ࣮ࣝࢶ ࢪ࣮ࣗࢫࡢᡂศࡀ CYP3A4 ࢆ㜼ᐖࡍࡿ ࡇࡼࡾࠊᮏࡢ⾑ ୰⃰ᗘࡀୖ᪼ࡍࡿࡇ ࡀ࠶ࡿࠋ ⸆≀௦ㅰ㓝⣲ 㸦CYP2C19㸧ࢆ㜼ᐖ ࡍࡿ⸆ ࣓࢜ࣉࣛࢰ࣮ࣝ➼ ᮏࡢస⏝ࡀቑᙉࡍ ࡿ࠾ࡑࢀࡀ࠶ࡿࠋే⏝ ࡍࡿሙྜࡣῶ㔞࠶ࡿ ࠸ࡣప⏝㔞ࡽ㛤ጞ ࡍࡿ࡞ὀពࡍࡿࡇ ࠋ ࡇ ࢀ ࡽ ࡢ ⸆ ࡀ CYP2C19 ࢆ㜼ᐖࡍࡿ ࡇࡼࡾࠊᮏࡢ⾑ ୰⃰ᗘࡀୖ᪼ࡍࡿࡇ ࡀ࠶ࡿࠋ 㸶㸬స⏝ 㸦㸯㸧స⏝ࡢᴫせ ᮏࡣࠊ⏝ᡂ⦼ㄪᰝ➼ࡢస⏝Ⓨ⌧㢖ᗘࡀ᫂☜࡞ࡿㄪᰝࢆᐇࡋ࡚࠸ ࡞࠸ࠋ 㸦㸰㸧㔜࡞స⏝ึᮇ≧ ࠺ࡗ⾑ᛶᚰࠊᚰ➽᱾ሰࠊ⊃ᚰࠊᚰᐊ㢖ᢿ ࠺ࡗ⾑ᛶᚰࠊᚰ 1㸧࠺ ➽᱾ሰࠊ⊃ᚰࠊᚰᐊ㢖ᢿࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊ␗ᖖࡀㄆࡵ ࡽࢀࡓሙྜࡣᢞࢆ୰Ṇࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 2㸧ฟ ฟ⾑ 㸺⬻ฟ⾑➼ࡢ㢌ෆฟ⾑㸼 ⬻ฟ⾑➼ࡢ㢌ෆฟ⾑㸦ึᮇ≧㸸㢌③ࠊᝏᚰ࣭ྤࠊព㆑㞀ᐖࠊ ∦㯞⑷➼㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࠋࡇࡢࡼ࠺࡞ሙྜࡣᢞࢆ୰ Ṇࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 㸺⫵ฟ⾑ࠊᾘ⟶ฟ⾑ࠊ㰯ฟ⾑ࠊ║ᗏฟ⾑➼㸼 ⫵ฟ⾑ࠊᾘ⟶ฟ⾑ࠊ㰯ฟ⾑ࠊ║ᗏฟ⾑➼ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࠋ ࡇࡢࡼ࠺࡞ሙྜࡣᢞࢆ୰Ṇࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 3㸧⫶ ⫶࣭༑ᣦ⭠₽⒆ ฟ⾑ࢆక࠺⫶࣭༑ᣦ⭠₽⒆ࡀ࠶ࡽࢃࢀࡿࡇࡀ ࠶ࡿࡢ࡛ࠊほᐹࢆ༑ศ⾜࠸ࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣᢞࢆ୰Ṇ ࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 4㸧ỗ ỗ⾑⌫ῶᑡࠊ↓㢛⢏⌫ࠊ⾑ᑠᯈῶᑡ ỗ⾑⌫ῶᑡࠊ↓㢛⢏⌫ࠊ⾑ ᑠᯈῶᑡࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊほᐹࢆ༑ศ⾜࠸ࠊ␗ᖖࡀㄆ ࡵࡽࢀࡓሙྜࡣᢞࢆ୰Ṇࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 5㸧㛫 㛫㉁ᛶ⫵⅖ Ⓨ⇕ࠊတႿࠊ྾ᅔ㞴ࠊ⬚㒊 X ⥺␗ᖖࠊዲ㓟⌫ቑከࢆక ࠺㛫㉁ᛶ⫵⅖ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࠋࡇࡢࡼ࠺࡞ሙྜࡣᢞࢆ୰ Ṇࡋࠊ⭈⓶㉁࣍ࣝࣔࣥࡢᢞ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 6㸧⫢ ⫢ᶵ⬟㞀ᐖࠊ㯤⑇ AST㸦GOT㸧 ࠊALT㸦GPT㸧 ࠊAl-PࠊLDH ➼ࡢୖ ᪼ࡸ㯤⑇ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊほᐹࢆ༑ศ⾜࠸ࠊ␗ᖖࡀㄆ ࡵࡽࢀࡓሙྜࡣᢞࢆ୰Ṇࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 7㸧ᛴ ᛴᛶ⭈ ᛴᛶ⭈ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊ⭈ᶵ⬟᳨ᰝࢆ ⾜࠺࡞ほᐹࢆ༑ศ⾜࠸ࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣᢞࢆ୰Ṇ ࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 㢖ᗘ᫂ 㸦㸱㸧ࡑࡢࡢస⏝ 㸨1 Ⓨ⑈ࠊ⓶⑈ࠊⶼ㯞⑈ࠊ⒍ឤࠊග⥺㐣ᩄࠊ⣚ᩬ➼ 㸨2 ືࠊ㢖⬦ࠊ࡚ࡾࠊ⾑ᅽୖ᪼ࠊᚰᡣ⣽ືࠊୖᐊᛶ㢖 ᢿࠊୖᐊᛶᮇእ⦰ࠊᚰᐊᛶᮇእ⦰➼ࡢᩚ⬦ࠊ⾑ ᅽపୗ➼ 㢌③࣭㢌㔜ឤࠊࡵࡲ࠸ࠊ╀ࠊࡋࡧࢀឤࠊ╀Ẽࠊᡓࠊ ⫪ࡇࡾࠊኻ⚄୍࣭㐣ᛶࡢព㆑ᾘኻ➼ 㐣ᩄ ᚠ⎔ჾ ⢭⚄⚄⤒⣔㸨2 ᾘჾ ⭡③ࠊᝏᚰ࣭ྤࠊ㣗ḧࠊୗ⑩ࠊ⬚ࡸࡅࠊ⭡㒊⭾ ‶ឤࠊぬ␗ᖖࠊཱྀῬ➼ ⾑ᾮ ㈋⾑ࠊⓑ⾑⌫ῶᑡࠊዲ㓟⌫ቑከ➼ ฟ⾑ഴྥ ⓶ୗฟ⾑ࠊ⾑ᒀ➼ ⫢⮚ AST㸦GOT㸧ࠊALT㸦GPT㸧 ࠊAl-PࠊLDH ࡢୖ᪼➼ ⭈⮚ BUN ୖ᪼ࠊࢡࣞࢳࢽࣥୖ᪼ࠊᒀ㓟್ୖ᪼ࠊ㢖ᒀࠊ ᒀ㞀ᐖ➼ ࡑࡢ Ⓨờࠊᾋ⭘ࠊ⬚③ࠊ⾑⢾ୖ᪼ࠊ⪥㬆ࠊ⑊③ࠊᛰឤࠊ ⬺ຊឤࠊ⤖⭷⅖ࠊⓎ⇕ࠊ⬺ẟࠊ➽③ 㸨1 ࡇࡢࡼ࠺࡞ሙྜࡣᢞࢆ୰Ṇࡍࡿࡇࠋ 㸨2 ࡇࡢࡼ࠺࡞ሙྜࡣῶ㔞ཪࡣᢞࢆ୰Ṇࡍࡿ࡞㐺ษ࡞ฎ⨨ࢆ⾜࠺ ࡇࠋ 㸦㸲㸧㡯┠ูస⏝Ⓨ⌧㢖ᗘ ヱᙜ㈨ᩱ࡞ࡋ ཬࡧ⮫ᗋ᳨ᰝ್␗ᖖ୍ぴ 㸦㸳㸧ᇶ♏ᝈࠊྜేࠊ㔜 ᗘཬࡧᡭ⾡ࡢ᭷↓➼ ヱᙜ㈨ᩱ࡞ࡋ ⫼ᬒูࡢస⏝Ⓨ⌧㢖ᗘ 㸦㸴㸧⸆≀ࣞࣝࢠ࣮ᑐࡍ ࡿὀពཬࡧヨ㦂ἲ ヱᙜ㈨ᩱ࡞ࡋ 㸷㸬㧗㱋⪅ࡢᢞ ୍⯡㧗㱋⪅࡛ࡣ⏕⌮ᶵ⬟ࡀపୗࡋ࡚࠸ࡿࡢ࡛ࠊῶ㔞ࡍࡿ࡞ὀពࡍࡿࡇ ࠋ 㸯㸮㸬ዷ፬ࠊ⏘፬ࠊᤵங፬➼ ࡢᢞ 㸦1㸧ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿ፬ேࡣᢞࡋ࡞࠸ࡇࠋ ࠝື≀ ᐇ㦂㸦ࣛࢵࢺ㸧࡛␗ᖖ⫾ඣࡢቑຍ୪ࡧฟ⏕ඣࡢపయ㔜ཬࡧṚஸඣࡢ ቑຍࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋࠞ 㸦2㸧ᤵங୰ࡢ፬ேࡣᮏᢞ୰ࡣᤵஙࢆ㑊ࡅࡉࡏࡿࡇࠋ ࠝື≀ᐇ㦂 㸦ࣛࢵࢺ㸧࡛ஙỒ୰ࡢ⛣⾜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ ࠞ 㸯㸯㸬ᑠඣ➼ࡢᢞ పฟ⏕య㔜ඣࠊ᪂⏕ඣࠊஙඣࠊᗂඣཪࡣᑠඣᑐࡍࡿᏳᛶࡣ☜❧ࡋ࡚࠸ ࡞࠸㸦⏝⤒㦂ࡀᑡ࡞࠸㸧 ࠋ 㸯㸰㸬⮫ᗋ᳨ᰝ⤖ᯝཬࡰࡍ ᙳ㡪 ヱᙜ㈨ᩱ࡞ࡋ 㸯㸱㸬㐣㔞ᢞ ヱᙜ㈨ᩱ࡞ࡋ 㸯㸲㸬㐺⏝ୖࡢὀព ⸆ PTPໟࡢ⸆ࡣPTPࢩ࣮ࢺࡽྲྀࡾฟࡋ࡚᭹⏝ࡍࡿࡼ࠺ ᣦᑟࡍࡿࡇࠋ ࠝPTPࢩ࣮ࢺࡢㄗ㣧ࡼࡾࠊ◳࠸㗦ゅ㒊ࡀ㣗㐨⢓⭷่ධ ࡋࠊ᭦ࡣ✸Ꮝࢆ㉳ࡇࡋ࡚⦪㝸Ὕ⅖➼ࡢ㔜⠜࡞ྜేࢆేⓎࡍࡿࡇࡀሗ ࿌ࡉࢀ࡚࠸ࡿࠋ ࠞ 㸯㸳㸬ࡑࡢࡢὀព 㸦1㸧ࢾࢆ⏝࠸ࡓ13㐌㛫⤒ཱྀᢞẘᛶヨ㦂ཬࡧ52㐌㛫⤒ཱྀᢞẘᛶヨ㦂 ࠾࠸࡚ࠊ㧗⏝㔞࡛ᕥᚰᐊᚰෆ⭷ࡢ⫧ཌཬࡧෙ≧ື⬦ኚࡀㄆࡵࡽ ࢀࠊ↓ẘᛶ㔞ࡣࡑࢀࡒࢀ30mg/kg/dayࠊ12mg/kg/day࡛࠶ࡗࡓࠋࣛࢵ ࢺཬࡧࢧ࡛ࣝࡣᚰ⮚ࡢኚࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ1㐌㛫㟼⬦ෆᢞᚰ ⮚ẘᛶヨ㦂࡛ࡣࠊࢾᕥᚰᐊᚰෆ⭷ࠊྑᚰᡣᚰእ⭷ཬࡧෙ≧ື⬦ࡢ ኚࡀࡳࡽࢀࠊࢧ࡛ࣝࡣ㍍ᗘࡢᕥᚰᐊᚰෆ⭷ࡢฟ⾑ᛶኚࡀㄆࡵࡽࢀ ࡓࠋࡢPDE㜼ᐖࡸ⾑⟶ᣑᙇ࠾࠸࡚ࡶື≀ᚰ⮚ẘᛶࡀㄆࡵࡽ ࢀ࡚࠾ࡾࠊ≉ࢾࡣⓎ⌧ࡋࡸࡍ࠸ື≀✀࡛࠶ࡿሗ࿌ࡉࢀ࡚࠸ࡿࠋ 㸦2㸧㑇ఏⓗⴭࡋࡃ㧗࠸⾑ᅽࡀᣢ⥆ࡋ⬻༞୰ࡀⓎࡍࡿࡉࢀ࡚࠸ࡿ SHR-SP㸦⬻༞୰᫆Ⓨ㧗⾑ᅽ⮬↛Ⓨࣛࢵࢺ㸧࠾࠸࡚ࠊࢩࣟࢫࢱ ࢰ࣮ࣝ0.3㸣ΰ㣵ᢞ⩌ࡣᑐ↷⩌ẚ㍑ࡋ࡚⏕Ꮡᮇ㛫ࡢ▷⦰ࡀㄆࡵࡽ ࢀࡓ㸦ᖹᆒᑑ㸸ࢩࣟࢫࢱࢰ࣮ࣝ⩌40.2㐌ࠊᑐ↷⩌43.5㐌㸧ࠋ 㸦3㸧♫ࡀᐇࡋࡓ⬻᱾ሰⓎᢚไຠᯝࢆ᳨ウࡍࡿヨ㦂࠾࠸࡚ࠊࢩࣟ ࢫࢱࢰ࣮ࣝ⩌⢾ᒀࡢⓎཬࡧᝏࡀከࡃࡳࡽࢀࡓࠋ 㸦4㸧ࢩࣟࢫࢱࢰ࣮ࣝ100mgHMG-CoA㑏ඖ㓝⣲㜼ᐖ⸆ࣟࣂࢫࢱࢳࣥ㸦ᅜ ෆᮍᢎㄆ㸧80mgࢆే⏝ᢞࡋࡓࡇࢁࠊࣟࣂࢫࢱࢳࣥ༢⊂ᢞẚ ࡚ࣟࣂࢫࢱࢳࣥࡢAUCࡀ64㸣ቑຍࡋࡓࡢᾏእሗ࿌ࡀ࠶ࡿࠋ 㸯㸴㸬ࡑࡢ ヱᙜࡋ࡞࠸ ,㹖㸬㠀⮫ᗋヨ㦂㛵ࡍࡿ㡯┠ 㸯㸬⸆⌮ヨ㦂 㸦㸯㸧⸆ຠ⸆⌮ヨ㦂 㸦 ࠕ㹔㹇㸬⸆ຠ⸆⌮㛵ࡍࡿ㡯┠ࠖࡢ㡯ཧ↷㸧 㸦㸰㸧ḟⓗ⸆⌮ヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧Ᏻᐃᛶ⸆⌮ヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸲㸧ࡑࡢࡢ⸆⌮ヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸰㸬ẘᛶ 㸦㸯㸧༢ᅇᢞẘᛶヨ㦂 ࢩࣟࢫࢱࢰ࣮ࣝࡢ LD50 ್㸦mg㸭kg㸧 ື≀㸦⣔⤫㸧 ᛶ LD60㸦⤒ཱྀ㸧 ࣐࢘ࢫ㸦ICR㸧 㞝 㸼5,000 㸦㸰㸧ᢞẘᛶヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸱㸧⏕ṪⓎ⏕ẘᛶヨ㦂 ヱᙜ㈨ᩱ࡞ࡋ 㸦㸲㸧ࡑࡢࡢ≉Ṧẘᛶ ヱᙜ㈨ᩱ࡞ࡋ 㹖㸬⟶⌮ⓗ㡯㛵ࡍࡿ㡯┠ 㸯㸬つไ༊ศ ヱᙜࡋ࡞࠸ 㸰㸬᭷ຠᮇ㛫ཪࡣ⏝ᮇ㝈 3 ᖺ㸦እ⟽⾲♧ࡢ⏝ᮇ㝈ෆ⏝ࡍࡿࡇࠋ 㸧 㸱㸬㈓ἲ࣭ಖᏑ᮲௳ ᐊ ಖᏑ 㸲㸬⸆ྲྀᢅ࠸ୖࡢὀពⅬ 㸦㸯㸧⸆ᒁ࡛ࡢྲྀࡾᢅ࠸ࡘ ࠸࡚ ヱᙜࡋ࡞࠸ 㸦㸰㸧⸆ࡢὀព㸦ᝈ ⪅➼␃ពࡍࡁᚲ㡲 㡯➼㸧 㸦 ࠕ㹔㹇㹇㹇㸬Ᏻᐃᛶ㸦⏝ୖࡢὀព➼㸧㛵ࡍࡿ㡯┠ 㸯㸲㸬㐺⏝ୖࡢ ὀពࠖࡢ㡯ཧ↷㸧 㸦㸱㸧ㄪࡢ␃ពⅬࡘ࠸࡚ ヱᙜࡋ࡞࠸ 㸳㸬ᢎㄆ᮲௳➼ ヱᙜࡋ࡞࠸ 㸴㸬ໟ 50mg 㸸 㸦PTP ໟ㸧100 㘄 100mg 㸸 㸦PTP ໟ㸧100 㘄 㸵㸬ᐜჾࡢᮦ㉁ 㹙PTP ໟရ㹛 PTP ໟ㸸ሷࣅࢽࣝࠊ࣑ࣝࢽ࣒࢘⟩ ෆ 㸸࣏࢚ࣜࢳࣞࣥࠊࢭࣟࢽ࣒࢘ እ ⟽㸸⣬ 㸶㸬ྠ୍ᡂศ࣭ྠຠ⸆ ࣉࣞࢱ࣮ࣝ㘄 㸦ሯ〇⸆㸧 㸷㸬ᅜ㝿ㄌ⏕ᖺ᭶᪥ ᫂ 㸯㸮㸬〇㐀㈍ᢎㄆᖺ᭶᪥ཬ ࡧᢎㄆ␒ྕ 50mg㸸 〇㐀㈍ᢎㄆᖺ᭶᪥㸸2009 ᖺ 7 ᭶ 13 ᪥ 〇㐀㈍ᢎㄆ ␒ ྕ㸸22100AMX01888000 100mg㸸 〇㐀㈍ᢎㄆᖺ᭶᪥㸸2000 ᖺ 2 ᭶ 18 ᪥ 〇㐀㈍ᢎㄆ ␒ ྕ㸸21200AMZ00097000 㸯㸯㸬⸆౯ᇶ‽㍕ᖺ᭶᪥ 50mg 㸸2009 ᖺ 11 ᭶ 13 ᪥ 100mg 㸸2000 ᖺ 7 ᭶ 7 ᪥ 㸯㸰㸬ຠ⬟ཪࡣຠᯝ㏣ຍࠊ⏝ ἲཬࡧ⏝㔞ኚ᭦࣭㏣ຍ➼ ࡢᖺ᭶᪥ཬࡧࡑࡢෆᐜ 50mg࣭100mg㸸2010 ᖺ 12 ᭶ 6 ᪥ ຠ⬟ཪࡣຠᯝ㸸⬻᱾ሰ㸦ᚰཎᛶ⬻ሰᰦࢆ㝖ࡃ㸧ⓎᚋࡢⓎᢚไࢆ㏣ຍ 㸯㸱㸬ᑂᰝ⤖ᯝࠊホ౯⤖ ᯝබ⾲ᖺ᭶᪥ཬࡧࡑࡢ ෆᐜ ヱᙜࡋ࡞࠸ 㸯㸲㸬ᑂᰝᮇ㛫 ヱᙜࡋ࡞࠸ 㸯㸳㸬ᢞᮇ㛫ᮇ㝈་⸆ရ 㛵ࡍࡿሗ ᮏࡣཌ⏕ປാ┬࿌♧➨ 97 ྕ㸦ᖹᡂ 20 ᖺ 3 ᭶ 19 ᪥㸧ࡼࡿࠕᢞᮇ 㛫ୖ㝈ࡀタࡅࡽࢀ࡚࠸ࡿ་⸆ရࠖヱᙜࡋ࡞࠸ࠋ 㸯㸴㸬ྛ✀ࢥ࣮ࢻ ཌ⏕┬⸆౯ᇶ‽㍕་⸆ရࢥ࣮ࢻ 50mg 㸸3399002F1222 100mg 㸸3399002F2075 㸯㸵㸬ಖ㝤⤥ୖࡢὀព ᮏࡣࠊಖ㝤デ⒪ୖࡢᚋⓎရ࡛࠶ࡿࠋ 㹖㹇㸬ᩥ⊩ 㸯㸬ᘬ⏝ᩥ⊩ 1㸧ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ᶆ‽〇ࡢ⏕≀Ꮫⓗྠ➼ᛶヨ㦂㸦ᑑ〇⸆ᰴ ᘧ♫♫ෆ㈨ᩱ㸧 2㸧ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࡢ⏕≀Ꮫⓗྠ➼ᛶヨ 㦂㸫⁐ฟヨ㦂㸫㸦ᑑ〇⸆ᰴᘧ♫♫ෆ㈨ᩱ㸧 3㸧ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ࡢ⁐ฟᣲື㸦ᑑ〇⸆ᰴᘧ♫♫ෆ㈨ᩱ㸧 4㸧ࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࡢ⁐ฟᣲື㸦ᑑ〇⸆ᰴᘧ♫♫ෆ㈨ᩱ㸧 5㸧ࢩࣟࢫࢱࢰ࣮ࣝࡢᢠ⾑ᑠᯈస⏝㸦ᑑ〇⸆ᰴᘧ♫♫ෆ㈨ᩱ㸧 6㸧ࢩࣟࢫࢱࢰ࣮ࣝࡢᢠ⾑ᰦస⏝㸦ᑑ〇⸆ᰴᘧ♫♫ෆ㈨ᩱ㸧 7㸧ࢥ࣮ࢺࣜࢬ࣒㘄 50mg ཬࡧࢥ࣮ࢺࣜࢬ࣒㘄 100mg ࡢᏳᐃᛶヨ㦂㸦ᑑ〇 ⸆ᰴᘧ♫♫ෆ㈨ᩱ㸧 㸰㸬ࡑࡢࡢཧ⪃ᩥ⊩ ࡞ࡋ 㹖,,㸬ཧ⪃㈨ᩱ 㸯㸬࡞እᅜ࡛ࡢⓎ≧ἣ ࡞ࡋ 㸰㸬ᾏእ࠾ࡅࡿ⮫ᗋᨭሗ ࡞ࡋ 㹖,,,㸬ഛ⪃ ࡑࡢࡢ㛵㐃㈨ᩱ ࡞ࡋ 〇㐀㈍ඖ ᑑ〇⸆ᰴᘧ♫