2016 ᖺ 2 ᭶ᨵゞ䠄ᨵゞ➨ 8 ∧䠅 ᪥ᮏᶆ‽ၟရศ㢮␒ྕ䠖871169 ་ ⸆ ရ 䜲䞁䝍䝡䝳䞊䝣䜷䞊䝮 ᪥ᮏ㝔⸆ᖌ䛾 IF グ㍕せ㡿 2013 䛻‽ᣐ䛧䛶సᡂ 䝟䞊䜻䞁䝋䞁 ⒪䠄㑅ᢥⓗ䠩䠝䠫--䠞㜼ᐖ䠅 ⸆ ぬ䛫䛔ཎᩱ ฎ᪉⟢་⸆ရ 䠄ὀព䠉་ᖌ➼䛾ฎ᪉⟢ 䛻䜘䜚⏝䛩䜛䛣䛸䠅 ᙧ FP--OD䠄䠄䝉䝺䜼䝸䞁ሷ㓟ሷཱྀ⭍ෆᔂቯ㘄䠅䠅 FP-O OD Tablet 2.5 ⣲㘄䠄ཱྀ⭍ෆᔂቯ㘄䠅 〇 䛾 つ ไ ༊ ศ ⸆䚸ぬ䛫䛔ཎᩱ䚸ฎ᪉⟢་⸆ရ䠄ὀព䠉་ᖌ➼䛾ฎ᪉⟢ 䛻䜘䜚⏝䛩䜛䛣䛸䠅 つ 㔞 1 㘄୰ 2.5mg ྡ ྡ䠖䝉䝺䜼䝸䞁ሷ㓟ሷ ὒྡ䠖Selegiline hydrochloride ୍ ᱁ 䞉 ⯡ ྵ 〇㐀㈍ᢎㄆᖺ᭶᪥ ⸆ ౯ ᇶ ‽ ㍕ 䞉 Ⓨ ᖺ ᭶ ᪥ 〇㐀㈍ᢎㄆᖺ᭶᪥䠖2007 ᖺ 3 ᭶ 15 ᪥ ⸆౯ᇶ‽㍕ᖺ᭶᪥䠖2007 ᖺ 7 ᭶ 6 ᪥ Ⓨ ᖺ ᭶ ᪥䠖2007 ᖺ 7 ᭶ 25 ᪥ 㛤Ⓨ䞉〇㐀㈍䠄㍺ධ䠅䞉 ᥦ ᦠ 䞉 ㈍ ♫ ྡ 〇㐀㈍ඖ䠖䜶䝣䝢䞊ᰴᘧ♫ ་⸆ሗᢸᙜ⪅䛾㐃⤡ඛ ၥ 䛔 ྜ 䜟 䛫 ❆ ཱྀ 䜶䝣䝢䞊ᰴᘧ♫ ་⸆Ꮫ⾡㒊 TEL 0120-545-427 FAX 0120-728-093 ཷ㛫 9:00䡚17:00 䠄ᅵ䞉᪥䞉⚃᪥䜢㝖䛟䠅 ་⒪㛵ಀ⪅ྥ䛡䝩䞊䝮䝨䞊䝆 http://www.fp-pharm.co.jp/ ᮏ IF 䛿 2015 ᖺ 12 ᭶ᨵゞ䛾ῧᩥ᭩䛾グ㍕䛻ᇶ䛵䛝ᨵゞ䛧䛯䚹 ᭱᪂䛾ῧᩥ᭩ሗ䛿䚸་⸆ရ་⒪ᶵჾሗᥦ౪䝩䞊䝮䝨䞊䝆 http://www.pmda.go.jp/safety/info-services/drugs/0001.html 䛻䛶䛤☜ㄆ䛟䛰䛥䛔䚹 IF ⏝䛾ᡭᘬ䛝䛾ᴫせ 䇷 ᪥ᮏ㝔⸆ᖌ 䇷 䠍䠊་⸆ရ䜲䞁䝍䝡䝳䞊䝣䜷䞊䝮సᡂ䛾⤒⦋ ་⒪⏝་⸆ရ䛾ᇶᮏⓗ䛺せ⣙ሗ䛸䛧䛶་⒪⏝་⸆ရῧᩥ᭩䠄௨ୗ䚸ῧᩥ᭩䛸␎䛩䠅䛜䛒䜛䚹་⒪ ⌧ሙ䛷་ᖌ䞉⸆ᖌ➼䛾་⒪ᚑ⪅䛜᪥ᖖᴗົ䛻ᚲせ䛺་⸆ရ䛾㐺ṇ⏝ሗ䜢ά⏝䛩䜛㝿䛻䛿䚸ῧ ᩥ᭩䛻グ㍕䛥䜜䛯ሗ䜢䛡䜛᭦䛻ヲ⣽䛺ሗ䛜ᚲせ䛺ሙྜ䛜䛒䜛䚹 ་⒪⌧ሙ䛷䛿䚸ᙜヱ་⸆ရ䛻䛴䛔䛶〇⸆ᴗ䛾་⸆ሗᢸᙜ⪅➼䛻ሗ䛾㏣ຍㄳồ䜔㉁䜢䛧䛶 ሗ䜢⿵䛧䛶ᑐฎ䛧䛶䛝䛶䛔䜛䚹䛣䛾㝿䛻ᚲせ䛺ሗ䜢⥙⨶ⓗ䛻ධᡭ䛩䜛䛯䜑䛾ሗ䝸䝇䝖䛸䛧䛶䜲䞁䝍䝡䝳 䞊䝣䜷䞊䝮䛜ㄌ⏕䛧䛯䚹 63 ᖺ䛻᪥ᮏ㝔⸆ᖌ䠄௨ୗ䚸᪥⸆䛸␎䛩䠅Ꮫ⾡➨ 2 ᑠጤဨ䛜䛂་⸆ရ䜲䞁䝍䝡䝳䞊䝣䜷䞊 䝮䛃䠄௨ୗ䚸IF 䛸␎䛩䠅䛾⨨䛡୪䜃䛻 IF グ㍕ᵝᘧ䜢⟇ᐃ䛧䛯䚹䛭䛾ᚋ䚸་⒪ᚑ⪅ྥ䛡୪䜃䛻ᝈ⪅ྥ䛡 ་⸆ရሗ䝙䞊䝈䛾ኚ䜢ཷ䛡䛶䚸ᖹᡂ 10 ᖺ 9 ᭶䛻᪥⸆Ꮫ⾡➨ 3 ᑠጤဨ䛻䛚䛔䛶 IF グ㍕せ㡿䛾ᨵ ゞ䛜⾜䜟䜜䛯䚹 ᭦䛻 10 ᖺ䛜⤒㐣䛧䛯⌧ᅾ䚸་⸆ရሗ䛾䜚ᡭ䛷䛒䜛〇⸆ᴗ䚸䛔ᡭ䛷䛒䜛་⒪⌧ሙ䛾⸆ᖌ䚸᪉ 䛻䛸䛳䛶⸆䞉་⒪⎔ቃ䛿䛝䛟ኚ䛧䛯䛣䛸䜢ཷ䛡䛶䚸ᖹᡂ 20 ᖺ 9 ᭶䛻᪥⸆་⸆ሗጤဨ䛻䛚䛔䛶 ᪂䛯䛺 IF グ㍕せ㡿䛜⟇ᐃ䛥䜜䛯䚹 IF グ㍕せ㡿 2008 䛷䛿䚸IF 䜢⣬፹య䛾Ꮚ䛸䛧䛶ᥦ౪䛩䜛᪉ᘧ䛛䜙䚸PDF ➼䛾㟁☢ⓗ䝕䞊䝍䛸䛧䛶ᥦ౪ 䛩䜛䛣䛸䠄e䠉IF䠅䛜ཎ๎䛸䛺䛳䛯䚹䛣䛾ኚ᭦䛻䛒䜟䛫䛶䚸ῧᩥ᭩䛻䛚䛔䛶䛂ຠ⬟䞉ຠᯝ䛾㏣ຍ䛃䚸䛂㆙࿌䞉⚗ ᚷ䞉㔜せ䛺ᇶᮏⓗὀព䛾ᨵゞ䛃䛺䛹䛾ᨵゞ䛜䛒䛳䛯ሙྜ䛻䚸ᨵゞ䛾᰿ᣐ䝕䞊䝍䜢㏣ຍ䛧䛯᭱᪂∧䛾 e䠉IF 䛜ᥦ౪䛥䜜䜛䛣䛸䛸䛺䛳䛯䚹 ᭱ ᪂ ∧ 䛾 e 䠉 IF 䛿 䚸 䠄 ⊂ 䠅 ་ ⸆ ရ ་ ⒪ ᶵ ჾ ⥲ ྜ ᶵ ᵓ 䛾 ་ ⸆ ရ ሗ ᥦ ౪ 䝩 䞊 䝮 䝨 䞊 䝆 䠄http://www.info.pmda.go.jp/䠅䛛䜙୍ᣓ䛧䛶ධᡭྍ⬟䛸䛺䛳䛶䛔䜛䚹᪥ᮏ㝔⸆ᖌ䛷䛿䚸e䠉IF 䜢ᥖ ㍕䛩䜛་⸆ရሗᥦ౪䝩䞊䝮䝨䞊䝆䛜බⓗ䝃䜲䝖䛷䛒䜛䛣䛸䛻㓄៖䛧䛶䚸⸆౯ᇶ‽㍕䛻䛒䜟䛫䛶 e䠉IF 䛾 ሗ䜢᳨ウ䛩䜛⤌⧊䜢タ⨨䛧䛶䚸ಶ䚻䛾 IF 䛜ῧᩥ᭩䜢⿵䛩䜛㐺ṇ⏝ሗ䛸䛧䛶㐺ษ䛛ᑂᰝ䞉᳨ウ䛩 䜛䛣䛸䛸䛧䛯䚹 ᖹᡂ 20 ᖺ䜘䜚ᖺ 4 ᅇ䛾䜲䞁䝍䝡䝳䞊䝣䜷䞊䝮᳨ウ䜢㛤ദ䛧䛯୰䛷ᣦ䛧䛶䛝䛯㡯䜢ホ౯䛧䚸〇⸆ ᴗ䛻䛸䛳䛶䜒䚸་ᖌ䞉⸆ᖌ➼䛻䛸䛳䛶䜒䚸ຠ⋡䛾Ⰻ䛔ሗ※䛸䛩䜛䛣䛸䜢⪃䛘䛯䚹䛭䛣䛷⯡䚸IF グ㍕せ㡿 䛾୍㒊ᨵゞ䜢⾜䛔 IF グ㍕せ㡿 2013 䛸䛧䛶බ⾲䛩䜛㐠䜃䛸䛺䛳䛯䚹 䠎䠊IF 䛸䛿 IF 䛿䛂ῧᩥ᭩➼䛾ሗ䜢⿵䛧䚸⸆ᖌ➼䛾་⒪ᚑ⪅䛻䛸䛳䛶᪥ᖖᴗົ䛻ᚲせ䛺䚸་⸆ရ䛾ရ㉁ ⟶⌮䛾䛯䜑䛾ሗ䚸ฎ᪉タィ䛾䛯䜑䛾ሗ䚸ㄪ䛾䛯䜑䛾ሗ䚸་⸆ရ䛾㐺ṇ⏝䛾䛯䜑䛾ሗ䚸⸆Ꮫⓗ 䛺ᝈ⪅䜿䜰䛾䛯䜑䛾ሗ➼䛜㞟⣙䛥䜜䛯⥲ྜⓗ䛺ಶู䛾་⸆ရゎㄝ᭩䛸䛧䛶䚸᪥⸆䛜グ㍕せ㡿䜢⟇ᐃ 䛧䚸⸆ᖌ➼䛾䛯䜑䛻ᙜヱ་⸆ရ䛾〇⸆ᴗ䛻సᡂཬ䜃ᥦ౪䜢౫㢗䛧䛶䛔䜛Ꮫ⾡㈨ᩱ䛃䛸⨨䛡䜙䜜䜛䚹 䛯䛰䛧䚸⸆ἲ䞉〇⸆ᴗᶵᐦ➼䛻㛵䜟䜛䜒䛾䚸〇⸆ᴗ䛾〇ດຊ䜢↓ຠ䛻䛩䜛䜒䛾ཬ䜃⸆ᖌ⮬䜙 䛜ホ౯䞉ุ᩿䞉ᥦ౪䛩䜉䛝㡯➼䛿 IF 䛾グ㍕㡯䛸䛿䛺䜙䛺䛔䚹ゝ䛔䛘䜛䛸䚸〇⸆ᴗ䛛䜙ᥦ౪䛥䜜䛯 IF 䛿䚸⸆ᖌ⮬䜙䛜ホ౯䞉ุ᩿䞉⮫ᗋ㐺ᛂ䛩䜛䛸䛸䜒䛻䚸ᚲせ䛺⿵䜢䛩䜛䜒䛾䛸䛔䛖ㄆ㆑䜢ᣢ䛴䛣䛸䜢๓ᥦ䛸䛧 䛶䛔䜛䚹 [IF 䛾ᵝᘧ]] 䐟 つ᱁䛿 A4 ∧䚸ᶓ᭩䛝䛸䛧䚸ཎ๎䛸䛧䛶 9 䝫䜲䞁䝖௨ୖ䛾Ꮠయ䠄ᅗ⾲䛿㝖䛟䠅䛷グ㍕䛧䚸୍Ⰽๅ䜚䛸䛩䜛䚹 䛯䛰䛧䚸ῧᩥ᭩䛷㉥ᯟ䞉㉥Ꮠ䜢⏝䛔䛯ሙྜ䛻䛿䚸㟁Ꮚ፹య䛷䛿䛣䜜䛻ᚑ䛖䜒䛾䛸䛩䜛䚹 䐠 IF グ㍕せ㡿䛻ᇶ䛵䛝సᡂ䛧䚸ྛ㡯┠ྡ䛿䝂䝅䝑䜽య䛷グ㍕䛩䜛䚹 䐡 ⾲⣬䛾グ㍕䛿⤫୍䛧䚸⾲⣬䛻⥆䛡䛶᪥⸆సᡂ䛾䛂IF ⏝䛾ᡭᘬ䛝䛾ᴫせ䛃䛾ᩥ䜢グ㍕䛩䜛䜒䛾 䛸䛧䚸2 㡫䛻䜎䛸䜑䜛䚹 [IF 䛾సᡂ] 䐟 IF 䛿ཎ๎䛸䛧䛶〇䛾ᢞ⤒㊰ู䠄ෆ⏝䚸ὀᑕ䚸እ⏝䠅䛻సᡂ䛥䜜䜛䚹 䐠 IF 䛻グ㍕䛩䜛㡯┠ཬ䜃㓄ิ䛿᪥⸆䛜⟇ᐃ䛧䛯 IF グ㍕せ㡿䛻‽ᣐ䛩䜛䚹 䐡 ῧᩥ᭩䛾ෆᐜ䜢⿵䛩䜛䛸䛾 IF 䛾᪨䛻ἢ䛳䛶ᚲせ䛺ሗ䛜グ㍕䛥䜜䜛䚹 䐢 〇⸆ᴗ䛾ᶵᐦ➼䛻㛵䛩䜛䜒䛾䚸〇⸆ᴗ䛾〇ດຊ䜢↓ຠ䛻䛩䜛䜒䛾ཬ䜃⸆ᖌ䜢䛿䛨䜑་⒪ᚑ ⪅⮬䜙䛜ホ౯䞉ุ᩿䞉ᥦ౪䛩䜉䛝㡯䛻䛴䛔䛶䛿グ㍕䛥䜜䛺䛔䚹 䐣 䛂་⸆ရ䜲䞁䝍䝡䝳䞊䝣䜷䞊䝮グ㍕せ㡿 2013䛃䠄௨ୗ䚸䛂IF グ㍕せ㡿 2013䛃䛸␎䛩䠅䛻䜘䜚సᡂ䛥䜜䛯 IF 䛿䚸㟁Ꮚ፹య䛷䛾ᥦ౪䜢ᇶᮏ䛸䛧䚸ᚲせ䛻ᛂ䛨䛶⸆ᖌ䛜㟁Ꮚ፹య䠄PDF䠅䛛䜙༳ๅ䛧䛶⏝䛩 䜛䚹ᴗ䛷䛾〇ᮏ䛿ᚲ㡲䛷䛿䛺䛔䚹 [IF 䛾Ⓨ⾜]] 䐟 䛂IF グ㍕せ㡿 2013䛃䛿䚸ᖹᡂ 25 ᖺ 10 ᭶௨㝆䛻ᢎㄆ䛥䜜䛯᪂་⸆ရ䛛䜙㐺⏝䛸䛺䜛䚹 䐠 ୖグ௨እ䛾་⸆ရ䛻䛴䛔䛶䛿䚸䛂IF グ㍕せ㡿 2013䛃䛻䜘䜛సᡂ䞉ᥦ౪䛿ᙉไ䛥䜜䜛䜒䛾䛷䛿䛺䛔䚹 䐡 ⏝ୖ䛾ὀព䛾ᨵゞ䚸ᑂᰝ⤖ᯝཪ䛿ホ౯⤖ᯝ䠄⮫ᗋホ౯䠅䛜බ⾲䛥䜜䛯Ⅼ୪䜃䛻㐺ᛂ䛾 ᣑ➼䛜䛺䛥䜜䚸グ㍕䛩䜉䛝ෆᐜ䛜䛝䛟ኚ䜟䛳䛯ሙྜ䛻䛿 IF 䛜ᨵゞ䛥䜜䜛䚹 䠏䠊IF 䛾⏝䛻䛒䛯䛳䛶 䛂IF グ㍕せ㡿 2013䛃䛻䛚䛔䛶䛿䚸PDF 䝣䜯䜲䝹䛻䜘䜛㟁Ꮚ፹య䛷䛾ᥦ౪䜢ᇶᮏ䛸䛧䛶䛔䜛䚹ሗ䜢⏝䛩 䜛⸆ᖌ䛿䚸㟁Ꮚ፹య䛛䜙༳ๅ䛧䛶⏝䛩䜛䛣䛸䛜ཎ๎䛷䛒䜛䚹 㟁Ꮚ፹య䛾 IF 䛻䛴䛔䛶䛿䚸་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ䛾་⸆ရ་⒪ᶵჾሗᥦ౪䝩䞊䝮䝨䞊䝆䛻ᥖ㍕ ሙᡤ䛜タᐃ䛥䜜䛶䛔䜛䚹 〇⸆ᴗ䛿䛂་⸆ရ䜲䞁䝍䝡䝳䞊䝣䜷䞊䝮సᡂ䛾ᡭᘬ䛝䛃䛻ᚑ䛳䛶సᡂ䞉ᥦ౪䛩䜛䛜䚸IF 䛾ཎⅬ䜢㋃䜎䛘䚸 ་⒪⌧ሙ䛻㊊䛧䛶䛔䜛ሗ䜔 IF సᡂ䛻グ㍕䛧㞴䛔ሗ➼䛻䛴䛔䛶䛿〇⸆ᴗ䛾 MR ➼䜈䛾䜲䞁䝍䝡 䝳䞊䛻䜘䜚⸆ᖌ➼⮬䜙䛜ෆᐜ䜢ᐇ䛥䛫䚸IF 䛾⏝ᛶ䜢㧗䜑䜛ᚲせ䛜䛒䜛䚹䜎䛯䚸㝶ᨵゞ䛥䜜䜛⏝ୖ 䛾ὀព➼䛻㛵䛩䜛㡯䛻㛵䛧䛶䛿䚸IF 䛜ᨵゞ䛥䜜䜛䜎䛷䛾㛫䛿䚸ᙜヱ་⸆ရ䛾〇⸆ᴗ䛜ᥦ౪䛩䜛ῧᩥ ᭩䜔䛚▱䜙䛫ᩥ᭩➼䚸䛒䜛䛔䛿་⸆ရ་⒪ᶵჾሗ㓄ಙ䝃䞊䝡䝇➼䛻䜘䜚⸆ᖌ➼⮬䜙䛜ᩚഛ䛩䜛䛸䛸䜒 䛻䚸IF 䛾⏝䛻䛒䛯䛳䛶䛿䚸᭱᪂䛾ῧᩥ᭩䜢་⸆ရ་⒪ᶵჾሗᥦ౪䝩䞊䝮䝨䞊䝆䛷☜ㄆ䛩䜛䚹 䛺䛚䚸㐺ṇ⏝䜔Ᏻᛶ䛾☜ಖ䛾Ⅼ䛛䜙グ㍕䛥䜜䛶䛔䜛䛂⮫ᗋᡂ⦼䛃䜔䛂䛺እᅜ䛷䛾Ⓨ≧ἣ䛃䛻㛵䛩 䜛㡯┠➼䛿ᢎㄆ㡯䛻㛵䜟䜛䛣䛸䛜䛒䜚䚸䛭䛾ྲྀᢅ䛔䛻䛿༑ศ␃ព䛩䜉䛝䛷䛒䜛䚹 䠐䠊⏝䛻㝿䛧䛶䛾␃ពⅬ IF 䜢⸆ᖌ➼䛾᪥ᖖᴗົ䛻䛚䛔䛶Ḟ䛛䛩䛣䛸䛜䛷䛝䛺䛔་⸆ရሗ※䛸䛧䛶ά⏝䛧䛶㡬䛝䛯䛔䚹䛧䛛䛧䚸 ⸆ἲ䜔་⒪⏝་⸆ရ䝥䝻䝰䞊䝅䝵䞁䝁䞊䝗➼䛻䜘䜛つไ䛻䜘䜚䚸〇⸆ᴗ䛜་⸆ရሗ䛸䛧䛶ᥦ౪䛷䛝䜛 ⠊ᅖ䛻䛿⮬䛪䛸㝈⏺䛜䛒䜛䚹IF 䛿᪥⸆䛾グ㍕せ㡿䜢ཷ䛡䛶䚸ᙜヱ་⸆ရ䛾〇⸆ᴗ䛜సᡂ䞉ᥦ౪䛩䜛䜒 䛾䛷䛒䜛䛣䛸䛛䜙䚸グ㍕䞉⾲⌧䛻䛿ไ⣙䜢ཷ䛡䛦䜛䜢ᚓ䛺䛔䛣䛸䜢ㄆ㆑䛧䛶䛚䛛䛺䛡䜜䜀䛺䜙䛺䛔䚹 䜎䛯〇⸆ᴗ䛿䚸IF 䛜䛒䛟䜎䛷䜒ῧᩥ᭩䜢⿵䛩䜛ሗ㈨ᮦ䛷䛒䜚䚸䜲䞁䝍䞊䝛䝑䝖䛷䛾බ㛤➼䜒㋃䜎 䛘䚸⸆ἲୖ䛾ᗈ࿌つไ䛻ゐ䛧䛺䛔䜘䛖␃ព䛧సᡂ䛥䜜䛶䛔䜛䛣䛸䜢⌮ゎ䛧䛶ሗ䜢ά⏝䛩䜛ᚲせ䛜䛒䜛䚹 䠄2013 ᖺ 4 ᭶ᨵゞ䠅 䠉 ┠ ḟ 䠉 䊠䠊ᴫせ䛻㛵䛩䜛㡯┠ .................................................................................................. 1 䠍䠊 㛤Ⓨ䛾⤒⦋ .............................................................................................................................. 1 䠎䠊 〇ရ䛾⒪Ꮫⓗ䞉〇Ꮫⓗ≉ᛶ ............................................................................................... 1 䊡䠊ྡ⛠䛻㛵䛩䜛㡯┠ .................................................................................................. 3 䠍䠊 ㈍ྡ ..................................................................................................................................... 3 䠎䠊 ୍⯡ྡ ..................................................................................................................................... 3 䠏䠊 ᵓ㐀ᘧཪ䛿♧ᛶᘧ ................................................................................................................... 3 䠐䠊 ศᏊᘧཬ䜃ศᏊ㔞 ................................................................................................................... 3 䠑䠊 Ꮫྡ䠄ྡἲ䠅....................................................................................................................... 3 䠒䠊 ័⏝ྡ䚸ูྡ䚸␎ྕ䚸グྕ␒ྕ ................................................................................................. 3 䠓䠊 䠟䠝䠯Ⓩ㘓␒ྕ ......................................................................................................................... 3 䊢䠊᭷ຠᡂศ䛻㛵䛩䜛㡯┠........................................................................................... 4 䠍䠊 ≀⌮Ꮫⓗᛶ㉁....................................................................................................................... 4 䠎䠊 ᭷ຠᡂศ䛾ྛ✀᮲௳ୗ䛻䛚䛡䜛Ᏻᐃᛶ.................................................................................... 5 䠏䠊 ᭷ຠᡂศ䛾☜ㄆヨ㦂ἲ ............................................................................................................ 6 䠐䠊 ᭷ຠᡂศ䛾ᐃ㔞ἲ ................................................................................................................... 6 䊣䠊〇䛻㛵䛩䜛㡯┠ .................................................................................................. 7 䠍䠊 ᙧ ......................................................................................................................................... 7 䠎䠊 〇䛾⤌ᡂ .............................................................................................................................. 7 䠏䠊 ᠱ⃮䚸ங䛾ศᩓᛶ䛻ᑐ䛩䜛ὀព ........................................................................................ 7 䠐䠊 〇䛾ྛ✀᮲௳ୗ䛻䛚䛡䜛Ᏻᐃᛶ ........................................................................................... 8 䠑䠊 ㄪ〇ἲཬ䜃⁐ゎᚋ䛾Ᏻᐃᛶ .................................................................................................... 9 䠒䠊 䛸䛾㓄ྜኚ䠄≀⌮Ꮫⓗኚ䠅 ....................................................................................... 9 䠓䠊 ⁐ฟᛶ ................................................................................................................................... 10 䠔䠊 ⏕≀Ꮫⓗヨ㦂ἲ......................................................................................................................11 䠕䠊 〇୰䛾᭷ຠᡂศ䛾☜ㄆヨ㦂ἲ ............................................................................................11 10䠊 〇୰䛾᭷ຠᡂศ䛾ᐃ㔞ἲ ....................................................................................................11 11䠊 ຊ౯ ........................................................................................................................................11 12䠊 ΰධ䛩䜛ྍ⬟ᛶ䛾䛒䜛ዃ㞧≀ ..................................................................................................11 13䠊 ὀព䛜ᚲせ䛺ᐜჾ䞉እほ䛜≉Ṧ䛺ᐜჾ䛻㛵䛩䜛ሗ ...............................................................11 14䠊 䛭䛾.....................................................................................................................................11 䊤䠊⒪䛻㛵䛩䜛㡯┠ ................................................................................................ 12 䠍䠊 ຠ⬟ཪ䛿ຠᯝ ........................................................................................................................ 12 䠎䠊 ⏝ἲཬ䜃⏝㔞 ........................................................................................................................ 12 䠏䠊 ⮫ᗋᡂ⦼ ............................................................................................................................... 12 䊥䠊⸆ຠ⸆⌮䛻㛵䛩䜛㡯┠......................................................................................... 17 䠍䠊 ⸆⌮Ꮫⓗ䛻㛵㐃䛒䜛ྜ≀ཪ䛿ྜ≀⩌ .............................................................................. 17 䠎䠊 ⸆⌮స⏝ ............................................................................................................................... 17 䊦䠊⸆≀ືែ䛻㛵䛩䜛㡯┠......................................................................................... 21 䠍䠊 ⾑୰⃰ᗘ䛾᥎⛣䞉 ᐃἲ ........................................................................................................ 21 䠎䠊 ⸆≀㏿ᗘㄽⓗ䝟䝷䝯䞊䝍 ......................................................................................................... 23 䠏䠊 ྾ ....................................................................................................................................... 24 䠐䠊 ศᕸ ....................................................................................................................................... 24 䠑䠊 ௦ㅰ ....................................................................................................................................... 26 䠒䠊 ἥ ....................................................................................................................................... 27 䠓䠊 䝖䝷䞁䝇䝫䞊䝍䞊䛻㛵䛩䜛ሗ................................................................................................. 27 䠔䠊 ㏱ᯒ➼䛻䜘䜛㝖ཤ⋡ ............................................................................................................... 27 䊧䠊Ᏻᛶ䠄⏝ୖ䛾ὀព➼䠅䛻㛵䛩䜛㡯┠ ................................................................ 28 1䠊 ㆙࿌ෆᐜ䛸䛭䛾⌮⏤ ............................................................................................................... 28 䠎䠊 ⚗ᚷෆᐜ䛸䛭䛾⌮⏤ ............................................................................................................... 28 䠏䠊 ຠ⬟ཪ䛿ຠᯝ䛻㛵㐃䛩䜛⏝ୖ䛾ὀព䛸䛭䛾⌮⏤................................................................. 29 䠐䠊 ⏝ἲཬ䜃⏝㔞䛻㛵㐃䛩䜛⏝ୖ䛾ὀព䛸䛭䛾⌮⏤................................................................. 29 䠑䠊 ៅ㔜ᢞෆᐜ䛸䛭䛾⌮⏤........................................................................................................ 29 䠒䠊 㔜せ䛺ᇶᮏⓗὀព䛸䛭䛾⌮⏤ཬ䜃ฎ⨨᪉ἲ ........................................................................... 30 䠓䠊 ┦స⏝ ............................................................................................................................... 31 䠔䠊 స⏝ ................................................................................................................................... 34 䠕䠊 㧗㱋⪅䜈䛾ᢞ ..................................................................................................................... 45 10䠊 ዷ፬䚸⏘፬䚸ᤵங፬➼䜈䛾ᢞ.............................................................................................. 45 11䠊 ᑠඣ➼䜈䛾ᢞ ..................................................................................................................... 46 12䠊 ⮫ᗋ᳨ᰝ⤖ᯝ䛻ཬ䜌䛩ᙳ㡪................................................................................................... 46 13䠊 㐣㔞ᢞ ............................................................................................................................... 46 14䠊 㐺⏝ୖ䛾ὀព ........................................................................................................................ 47 15䠊 䛭䛾䛾ὀព ......................................................................................................................... 47 16䠊 䛭䛾.................................................................................................................................... 47 䊨䠊㠀⮫ᗋヨ㦂䛻㛵䛩䜛㡯┠ ..................................................................................... 48 䠍䠊 ⸆⌮ヨ㦂 ............................................................................................................................... 48 䠎䠊 ẘᛶヨ㦂 ............................................................................................................................... 49 䊩䠊⟶⌮ⓗ㡯䛻㛵䛩䜛㡯┠ ..................................................................................... 51 䠍䠊 つไ༊ศ ............................................................................................................................... 51 䠎䠊 ᭷ຠᮇ㛫ཪ䛿⏝ᮇ㝈 .......................................................................................................... 51 䠏䠊 ㈓ἲ䞉ಖᏑ᮲௳ ...................................................................................................................... 51 䠐䠊 ⸆ྲྀᢅ䛔ୖ䛾ὀពⅬ .......................................................................................................... 51 䠑䠊 ᢎㄆ᮲௳➼ ............................................................................................................................ 52 䠒䠊 ໟ ....................................................................................................................................... 52 䠓䠊 ᐜჾ䛾ᮦ㉁ ............................................................................................................................ 52 䠔䠊 ྠ୍ᡂศ䞉ྠຠ⸆ ................................................................................................................... 52 䠕䠊 ᅜ㝿ㄌ⏕ᖺ᭶᪥..................................................................................................................... 52 10䠊 〇㐀㈍ᢎㄆᖺ᭶᪥ཬ䜃ᢎㄆ␒ྕ ....................................................................................... 52 11䠊 ⸆౯ᇶ‽㍕ᖺ᭶᪥ ............................................................................................................. 52 12䠊 ຠ⬟ཪ䛿ຠᯝ㏣ຍ䚸⏝ἲཬ䜃⏝㔞ኚ᭦㏣ຍ➼䛾ᖺ᭶᪥ཬ䜃䛭䛾ෆᐜ................................... 52 13䠊 ᑂᰝ⤖ᯝ䚸ホ౯⤖ᯝබ⾲ᖺ᭶᪥ཬ䜃䛭䛾ෆᐜ................................................................ 53 14䠊 ᑂᰝᮇ㛫 ............................................................................................................................ 53 15䠊 ᢞ⸆ᮇ㛫ไ㝈་⸆ရ䛻㛵䛩䜛ሗ ........................................................................................ 53 16䠊 ྛ✀䝁䞊䝗.............................................................................................................................. 53 17䠊 ಖ㝤⤥ୖ䛾ὀព ................................................................................................................. 53 䊪䠊ᩥ⊩ .................................................................................................................... 54 䠍䠊 ᘬ⏝ᩥ⊩ ............................................................................................................................... 54 䠎䠊 䛭䛾䛾ཧ⪃ᩥ⊩.................................................................................................................. 56 䠏䠊 ᩥ⊩ㄳồඛ ............................................................................................................................ 56 䊫䠊ཧ⪃㈨ᩱ ............................................................................................................. 57 䊩䊢䠊ഛ⪃ ................................................................................................................... 58 䊠䠊ᴫせ䛻㛵䛩䜛㡯┠ 䠍䠊 㛤Ⓨ䛾⤒⦋ 䝉䝺䜼䝸䞁ሷ㓟ሷ䠄㏻⛠䠖"-deprenyl䠅䛿䝝䞁䜺䝸䞊䛾⸆⌮Ꮫ⪅ J.Knoll 䛜 1964 ᖺ䛻Ⓨぢ䛧䛯ྍ ㏫ⓗ䛷㑅ᢥⓗ䛺 B ᆺ䝰䝜䜰䝭䞁㓟㓝⣲䠄MAO-B䠅䛾㜼ᐖ䛷䛒䜛 1,2)䚹 1975 ᖺ䛻ึ䜑䛶䜸䞊䝇䝖䝸䜰䛷䝺䝪䝗䝟⒪䜢ཷ䛡䛶䛔䜛䝟䞊䜻䞁䝋䞁ᝈ⪅䛻䝉䝺䜼䝸䞁ሷ㓟ሷ 䜢㐺⏝ 3)䛧䛶௨᮶䚸ྛᅜ䛷ᩘከ䛟䛾⮫ᗋヨ㦂䛜ᐇ䛥䜜䚸ᮏ䛿䝺䝪䝗䝟䛷䛾⒪ຠᯝ䛜༑ศ 䛺䝟䞊䜻䞁䝋䞁ᝈ⪅䛻ᑐ䛧䛶䚸䛭䛾≧䛾᪥ෆኚື䜔䝟䞊䜻䞁䝋䝙䝈䝮䛾ᨵၿ䛻᭷⏝䛷䛒䜛䛸 ㄆ䜑䜙䜜䛯䚹 ᮏ㑥䛷䛿 1998 ᖺ 7 ᭶䛻䛂䜶䝣䝢䞊㘄 2.5䛃䛸䛧䛶ᢎㄆ䛥䜜䛯䛜䚸䝟䞊䜻䞁䝋䞁ᝈ⪅䛿㧗㱋⪅䛜ከ 䛟䚸᭹⏝䛧䜔䛩䛔〇䛜ᮃ䜎䜜䛶䛔䛯䚹䛭䛣䛷㧗㱋⪅䛷䜒᭹⏝䛜ᐜ᫆䛷䚸Ỉ䛺䛧䛷䜒᭹⏝ྍ⬟䛺ཱྀ ⭍ෆᔂቯ㘄䛾㛤Ⓨ䛻╔ᡭ䛧䚸2007 ᖺ 3 ᭶䛻䜶䝣䝢䞊㘄 2.5 䛸⏕≀Ꮫⓗ䛻ྠ➼䛺〇䛸䛧䛶䛂䜶䝣 䝢䞊OD 㘄 2.5䛃䛜ᢎㄆ䛥䜜䛯䚹 䜎䛯䚸䜶䝣䝢䞊㘄 2.5 䛿ᅜ 490 タ䛛䜙 4,717 䜢㞟䛧䚸᭷ຠᛶゎᯒᑐ㇟ 4,328 䚸Ᏻ ᛶゎᯒᑐ㇟ 4,692 䛾⏝ᡂ⦼ㄪᰝ䛾⤖ᯝ䜢ᇶ䛻䚸2004 ᖺ 9 ᭶䛻ᑂᰝ⏦ㄳ䜢⾜䛳䛯䚹 䛭䛾⤖ᯝ䚸2009 ᖺ 12 ᭶䛻⸆ἲ➨ 14 ᮲➨ 2 㡯ྛྕ䠄ᢎㄆᣄྰ⏤䠅䛾䛔䛪䜜䛻䜒ヱᙜ䛧䛺䛔 䛸䛾ᑂᰝ⤖ᯝ䜢ᚓ䛯䚹 2015 ᖺ 12 ᭶䚸᪩ᮇ䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯⮫ᗋヨ㦂䛻䛚䛔䛶ᮏ䛾༢⊂⒪ἲ䛻䛚䛡䜛 ᭷ຠᛶཬ䜃Ᏻᛶ䛜ㄆ䜑䜙䜜䚸༢⊂⒪ἲ䜢ྵ䜐䝺䝪䝗䝟ྵ᭷〇㠀ే⏝䛷䛾ᢞ䛜ຠ⬟㏣ຍ䛥 䜜䛯䚹 䠎䠊 〇ရ䛾⒪Ꮫⓗ䞉〇Ꮫⓗ≉ᛶ (1) ⬻䛾㯮㉁-⥺᮲య䛻䛚䛡䜛䝗䝟䝭䞁సືᛶ䝙䝳䞊䝻䞁䛛䜙㐟㞳䛥䜜䛯䝗䝟䝭䞁䛿 MAO䈜䠄䝰䝜䜰䝭䞁 㓟㓝⣲䠅䛻䜘䛳䛶ศゎ䛥䜜䜛䛜䚸䝠䝖䛾ሙྜ䚸⬻ෆ䛻䛿 B ᆺ䛾Ꮡᅾẚ䛜 85䠂䛸㧗䛟䚸䝗䝟䝭䞁䛿 䛻 MAO-B 䛻䜘䛳䛶ศゎ䛥䜜䛶䛔䜛 4,5)䚹MAO-B 䛾㑅ᢥⓗ㜼ᐖ䛷䛒䜛ᮏ䛿䚸䝗䝟䝭䞁䛾ῶ ᑡ䛧䛶䛔䜛䝟䞊䜻䞁䝋䞁ᝈ⪅䛾⬻ෆ MAO-B 䜢㜼ᐖ䛧䛶䚸䝅䝘䝥䝇㛫㝽䛾䝗䝟䝭䞁㔞䛾ῶᑡ䜢 ᢚไ䛩䜛䚹䜎䛯䚸䝅䝘䝥䝇䜈䛾䝗䝟䝭䞁䛾ྲྀ䜚㎸䜏㜼ᐖస⏝䛻䛶䚸䝗䝟䝭䞁㔞䛾ῶᑡ䜢䛥䜙䛻ᢚ ไ䛩䜛䚹䠄P.17䡚20 ཧ↷䠅 MAO 䛻䛿ᇶ㉁≉␗ᛶ䛾㐪䛔䛛䜙 A ᆺ䛸 B ᆺ䛾 2 䛴䛾䝃䝤䝍䜲䝥䛜䛒䜛䚹 䈜 (2) 䝺䝪䝗䝟ྵ᭷〇䛸䛾ే⏝⒪ἲ䛻䜘䜚䚸䝗䝟䝭䞁ᶵ⬟䜢ቑᙉ䞉ᣢ⥆䛩䜛䚹䛭䛾⤖ᯝ䚸䝟䞊䜻䞁䝋䞁 ≧䠄ᅛ⦰䚸↓ື䚸wearing off ⌧㇟➼䠅䛾ᨵၿ䚸䝺䝪䝗䝟㔞䛾ῶ㔞䛜ྍ⬟䛷䛒䛳䛯䚹ᮏ䛾༢ ⊂⒪ἲ䛷䛿䚸᪩ᮇ䝟䞊䜻䞁䝋䞁䛻䛚䛡䜛㐠ື≧䜔᪥ᖖ⏕άືస䜢ᨵၿ䛧䚸䛭䛾᭷ຠᛶ䛿ᢞ 㛤ጞᚋ 56 㐌䜎䛷⥔ᣢ䛥䜜䜛䛣䛸䛜☜ㄆ䛥䜜䛯䚹䠄P.12~16 ཧ↷䠅 (3) ᚑ᮶䛾㠀㑅ᢥⓗ MAO 㜼ᐖ䛷䜏䜙䜜䜛䝏䞊䝈ຠᯝ䜢♧䛥䛺䛔 6)䚹 (4) 䜶䝣䝢䞊OD 㘄 2.5 䛿ཱྀ⭍ෆ䛷㏿䜔䛛䛻ᔂቯ䛩䜛䛣䛸䛻䜘䜚䚸Ỉ䛺䛧䛷䜒᭹⏝ྍ⬟䛷䛒䜛䚹 䠄P.21~22 ཧ↷䠅 1 (5) 䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䛻䛚䛡䜛స⏝Ⓨ⌧⋡䛿 36.3䠂䠄177 /488 䠅䛷䛒䜚䚸ᝏᚰ䞉ྤ䚸䝆䝇䜻䝛䝆䜰䚸ᗁぬ䚸㣗ḧ䚸䜑䜎䛔䞉䜅䜙䛴䛝䛺䛹䛜ㄆ䜑䜙䜜 䛯䚹⮫ᗋ᳨ᰝ್䛾䛺␗ᖖኚື䛸䛧䛶䛿䚸CK䠄CPK䠅䛾ୖ᪼䚸LDH 䛾ୖ᪼䚸Al-P 䛾ୖ᪼䛜ሗ࿌ 䛥䜜䛶䛔䜛䠄䜶䝣䝢䞊㘄 2.5 ᢎㄆ䠅7䡚13)䚹 䜎䛯䚸䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯⏝ᡂ⦼ㄪᰝ䛻䛚䛡 䜛స⏝Ⓨ⌧⋡䛿 20.4䠂䠄957 /4,692 䠅䛷䛒䜚䚸ᗁぬ䚸ᝏᚰ䚸䝆䝇䜻䝛䝆䜰䚸䜑䜎䛔䚸㣗ḧ 䛺䛹䛜ㄆ䜑䜙䜜䛯䠄䜶䝣䝢䞊㘄 2.5 ᑂᰝ⤊䠅䚹 䛥䜙䛻䚸䝺䝪䝗䝟ྵ᭷〇㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䛻䛚䛡䜛స⏝Ⓨ⌧⋡䛿 40.4䠂䠄132 /327 䠅䛷䛒䜚䚸౽⛎䚸╀䚸㧗⾑ᅽ䚸CK䠄CPK䠅ୖ᪼䚸╀Ẽ䛺䛹䛜ㄆ䜑䜙䜜䛯䠄䜶䝣䝢䞊OD 㘄 2.5 ຠ⬟㏣ຍᢎㄆ䠅14䡚16䠅䚹 㔜䛺స⏝䛸䛧䛶䚸ᗁぬ䚸ዶ䚸㘒䚸䛫䜣ዶ䚸⊃ᚰ䚸ᝏᛶೃ⩌䚸ప⾑⢾䚸⫶₽⒆䛺䛹䛜 ሗ࿌䛥䜜䛶䛔䜛䚹䠄P.34䡚45 ཧ↷䠅 2 䊡䠊ྡ⛠䛻㛵䛩䜛㡯┠ 䠍䠊 ㈍ྡ (1) ྡ 䜶䝣䝢䞊OD 㘄 2.5 (2) ὒྡ FP-OD Tablet 2.5 (3) ྡ⛠䛾⏤᮶ Fujimoto·s anti-parkinson drug 䛸 Oral disintegrated formula 䛛䜙ྡ䛡䛯䚹 䠎䠊 ୍⯡ྡ (1) ྡ䠄ྡἲ䠅 䝉䝺䜼䝸䞁ሷ㓟ሷ䠄JAN䠅 (2) ὒྡ䠄ྡἲ䠅 Selegiline hydrochloride䠄JAN䠅䚸Selegiline䠄INN䠅 (3) 䝇䝔䝮䠄stem䠅 MAO-B 㜼ᐖ䠖 䠉giline 䠏䠊 ᵓ㐀ᘧཪ䛿♧ᛶᘧ H CH3 C CH2 N CH2C䍵CH 䞉HCl CH3 䠐䠊 ศᏊᘧཬ䜃ศᏊ㔞 ศᏊᘧ䠖C13H17N䡡HCl ศᏊ㔞䠖223.74 䠑䠊 Ꮫྡ䠄ྡἲ䠅 (䌦)-(R)-N,ǂ-dimethyl-N-2-propynylphenethylamine monohydrochloride䠄IUPAC䠅 䠒䠊 ័⏝ྡ䚸ูྡ䚸␎ྕ䚸グྕ␒ྕ ័⏝ྡ䠖"-deprenyl䠄"-䝕䝥䝺䝙䝹䠅 㦂␒ྕ䠖FPF1100NW 䠓䠊 䠟䠝䠯Ⓩ㘓␒ྕ 14611-52-0䠄䝉䝺䜼䝸䞁ሷ㓟ሷ䠅䚸14611-51-9䠄䝉䝺䜼䝸䞁䠅 3 䊢䠊᭷ຠᡂศ䛻㛵䛩䜛㡯┠ 䠍䠊 ≀⌮Ꮫⓗᛶ㉁ (1) እほ䞉ᛶ≧ ⓑⰍ䛾⤖ᬗᛶ䛾⢊ᮎ䛷䛒䜛䚹 (2) ⁐ゎᛶ 1) ྛ✀⁐፹䛻䛚䛡䜛⁐ゎᗘ 1g 䜢⁐䛛䛩䛾䛻 せ䛩䜛⁐፹㔞䠄mL䠅 ᪥ᮏ⸆ᒁ᪉䛾 ⁐ゎᗘ⾲グ 0.5䡚0.6 ᴟ䜑䛶⁐䛡䜔䛩䛔 0.9 ᴟ䜑䛶⁐䛡䜔䛩䛔 4 ⁐䛡䜔䛩䛔 㓑㓟䠄100䠅 1.6䡚1.7 ⁐䛡䜔䛩䛔 ↓Ỉ㓑㓟 52䡚54 䜔䜔⁐䛡䛻䛟䛔 䜰䝉䝖䞁 52䡚54 䜔䜔⁐䛡䛻䛟䛔 㓑㓟䜶䝏䝹 䠚10,000 䜋䛸䜣䛹⁐䛡䛺䛔 䝆䜶䝏䝹䜶䞊䝔䝹 䠚10,000 䜋䛸䜣䛹⁐䛡䛺䛔 ⁐፹ྡ Ỉ 䝯䝍䝜䞊䝹 䜶䝍䝜䞊䝹䠄95䠅 2) ྛ✀ pH ⁐፹䛻ᑐ䛩䜛⁐ゎᗘ pH䈜 ⁐ゎᗘ䠄mg/mL䠅 ⁐ゎᾮ䛾 pH 3 795.8 2.7 5 775.9 3.4 7 745.7 3.7 9 1.509 7.4 11 0.726 9.0 Britton-Robinson ⦆⾪ᾮ䜢⏝䛔䛯䚹 䈜 3) ྛ✀⁐፹䛻䛚䛡䜛㐟㞳ሷᇶ䛾⁐ゎᗘ 1g 䜢⁐䛛䛩䛾䛻せ䛩䜛 ⁐፹㔞䠄mL䠅 ᪥ᮏ⸆ᒁ᪉䛾⁐ゎᗘ⾲グ 䜶䝍䝜䞊䝹䠄99.5䠅 <1 ᴟ䜑䛶⁐䛡䜔䛩䛔 䜶䝍䝜䞊䝹䠄95䠅 <1 ᴟ䜑䛶⁐䛡䜔䛩䛔 䝖䝹䜶䞁 <1 ᴟ䜑䛶⁐䛡䜔䛩䛔 㓑㓟䜶䝏䝹 <1 ᴟ䜑䛶⁐䛡䜔䛩䛔 ⁐፹ྡ (3) ྾‵ᛶ ྾‵ᛶ䛿ㄆ䜑䜙䜜䛺䛔䠄40䉝/75䠂RH ཪ䛿 40䉝/90䠂RH 䛷 30 ᪥㛫䠅䚹 4 (4) ⼥Ⅼ䠄ศゎⅬ䠅䚸ἛⅬ䚸จᅛⅬ ⼥Ⅼ䠖140䡚144䉝 (5) 㓟ሷᇶゎ㞳ᐃᩘ pKa䠖7.40 (6) ศ㓄ಀᩘ ヨ㦂ᾮ ศ㓄ಀᩘ䠄1-䜸䜽䝍䝜䞊䝹/Ỉ⣔䠅 Ỉ 0.155 pH3.0 0.0418 pH5.0 2.00 pH7.0 737 pH9.0 749 (7) 䛭䛾䛾䛺♧ᛶ್ 1% ྾ගᗘ E1cm 䠄258nm䠅䠖7.7䡚8.2 䠄⇱ᚋ䚸50mg䚸Ỉ䚸100mL䠅 ᪕ගᗘ 䠷䃐䠹 20 D 䠙䠉10.0䡚䠉13.0㼻䠄⇱ᚋ䚸1g䚸Ỉ䚸10mL䚸100mm䠅 pH䠖4.0䡚4.6 䠄ᮏရ 0.2g 䜢Ỉ 10mL 䛻⁐䛛䛧䛶 ᐃ䠅 䠎䠊 ᭷ຠᡂศ䛾ྛ✀᮲௳ୗ䛻䛚䛡䜛Ᏻᐃᛶ (1) 㛗ᮇಖᏑヨ㦂 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 25䉝 39 䞃᭶ ᐦᰦ ᬯᡤ ኚ䛺䛧 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 50䉝 60䉝 60 ᪥ ᐦᑒ ᬯᡤ ኚ䛺䛧 ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 60 ᪥ 㛤ᰦ ᬯᡤ 15 ᪥┠௨㝆䛷ᛶ≧䛾ኚ 䠄จ㞟ሢኚ䠅䜢ㄆ䜑䛯䚹 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 䝣䜵䞊䝗䝯䞊䝍 䠄360,000lux䡡hr/᪥䠅 30 ᪥ 䝅䝱䞊䝺 ኚ䛺䛧 (2) ⱔ㓞ヨ㦂 ᗘ䛻ᑐ䛩䜛Ᏻᐃᛶ ‵ᗘ䛻ᑐ䛩䜛Ᏻᐃᛶ ಖᏑ᮲௳ 25䉝/75䠂RH 25䉝/90䠂RH 40䉝/75䠂RH 40䉝/90䠂RH ග䛻ᑐ䛩䜛Ᏻᐃᛶ 5 䠏䠊 ᭷ຠᡂศ䛾☜ㄆヨ㦂ἲ (1) ➨ 3 ⣭䜰䝭䞁 䜿䜲䝍䞁䜾䝇䝔䞁㓟⁐ᾮ䛸ᛂ䛧䛶ⓑⰍ䛾ỿẊ䜢⏕䛨䜛䚹 (2) 䝥䝻䝢䝙䝹ᇶ 䜲䝻䝇䝧䞊⁐ᾮ䛻䜘䜚㯤Ⰽ䛾ỿẊ䜢⏕䛨䜛䚹 (3) ⣸እ྾䝇䝨䜽䝖䝹 Ἴ㛗 251䡚254nm䚸256䡚259nm ཬ䜃 262䡚265nm 䛻྾䛾ᴟ䜢♧䛩䚹 (4) ㉥እ྾䝇䝨䜽䝖䝹 Ἴᩘ 3,220cm-1䚸2,930cm-1䚸2,120cm-1 ཬ䜃 1,598cm-1 ㏆䛻྾䜢ㄆ䜑䜛䚹 (5) ሷ≀ ᪥ᮏ⸆ᒁ᪉䛂ሷ≀䛾ᐃᛶᛂ䛃䛻䜘䜛䚹 䠐䠊 ᭷ຠᡂศ䛾ᐃ㔞ἲ 㟁ᕪᐃἲ䛻䜘䜚ᐃ㔞䛩䜛䚹 6 䊣䠊〇䛻㛵䛩䜛㡯┠ 䠍䠊 ᙧ (1) ᙧ䛾༊ู䚸እほཬ䜃ᛶ≧ ⓑⰍ䡚ᚤ㯤Ⰽ䛾⣲㘄䛷ῐ㯤Ⰽ䡚㯤Ⰽ䛾ᩬⅬ䛜䛒䜛䠄ཱྀ⭍ෆᔂቯ㘄䠅䚹 ၟရྡ ⾲㠃 㠃 ഃ㠃 䜶䝣䝢䞊OD 㘄 2.5 ┤ᚄ䠖7.5mm䚸ཌ䛥䠖4.2mm䚸㔜䛥䠖0.16g (2) 〇䛾≀ᛶ ᔂቯᛶ 䠖 ᪥ᮏ⸆ᒁ᪉䞉୍⯡ヨ㦂ἲ䛂ᔂቯヨ㦂ἲ ༶ᨺᛶ〇䛃䛾㡯䛻䜘䜚ヨ㦂䜢⾜䛖䛸䛝䚸䛣䜜䛻 㐺ྜ䛩䜛䚹 (3) ㆑ู䝁䞊䝗 FP-OD2.5 䠄PTP 䝅䞊䝖䛻⾲♧䠅 (4) pH䚸ᾐ㏱ᅽẚ䚸⢓ᗘ䚸ẚ㔜䚸↓⳦䛾᪨ཬ䜃Ᏻᐃ䛺 pH ᇦ➼ ヱᙜ䛧䛺䛔䚹 䠎䠊 〇䛾⤌ᡂ (1) ᭷ຠᡂศ䠄άᛶᡂศ䠅䛾ྵ㔞 1 㘄୰䛻䝉䝺䜼䝸䞁ሷ㓟ሷ䜢 2.5mg ྵ᭷䛩䜛䚹 (2) ῧຍ≀ ῧຍ≀䛸䛧䛶䝉䝹䝻䞊䝇䚸䝠䝗䝻䜻䝅䝥䝻䝢䝹䝉䝹䝻䞊䝇䚸䝠䝥䝻䝯䝻䞊䝇䚸D-䝬䞁䝙䝖䞊䝹䚸㓟䝏 䝍䞁䚸䝍䝹䜽䚸䝉䝍䝜䞊䝹䚸䝷䜴䝸䝹◲㓟䝘䝖䝸䜴䝮䚸ங⢾Ỉ≀䚸㯤Ⰽ୕㓟㕲䚸䜰䝇䝟䝹䝔䞊 䝮䚸䝇䝔䜰䝸䞁㓟䝬䜾䝛䝅䜴䝮䚸䛭䛾 7 ᡂศ䜢ྵ᭷䛩䜛䚹 (3) 䛭䛾 ヱᙜ䛧䛺䛔䚹 䠏䠊 ᠱ⃮䚸ங䛾ศᩓᛶ䛻ᑐ䛩䜛ὀព ヱᙜ䛧䛺䛔䚹 7 䠐䠊 〇䛾ྛ✀᮲௳ୗ䛻䛚䛡䜛Ᏻᐃᛶ (1) 㛗ᮇಖᏑヨ㦂 17䠅 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ 25䉝/60䠂RH 36 䞃᭶ PTP ໟ 䜰䝹䝭䝙䜴䝮⿄ ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ 40䉝/75䠂RH 6 䞃᭶ PTP ໟ 䜰䝹䝭䝙䜴䝮⿄ ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ 50䉝 4㐌 60䉝 4㐌 25䉝/90䠂RH 4㐌 ⤖ᯝ ኚ䛺䛧䚹 (2) ຍ㏿ヨ㦂 17䠅 ⤖ᯝ ኚ䛺䛧䚹 (3) ⱔ㓞ヨ㦂 17䠅 PTP ໟ 䜰䝹䝭䝙䜴䝮⿄ PTP ໟ 䜰䝹䝭䝙䜴䝮⿄ 〓Ⰽ䜺䝷䝇⎼ 䠄㛤ᨺ䠅 ⤖ᯝ ኚ䛺䛧䚹 ኚ䛺䛧䚹 ◳ᗘ䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾㡯┠䛿ኚ䛺䛧䚹 (4) 䛭䛾ྛ✀᮲௳ୗ䛷䛾Ᏻᐃᛶヨ㦂 1) PTP ໟ䛾Ᏻᐃᛶヨ㦂 18䠅 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 25䉝/60䠂RH 6 䞃᭶ PTP ໟ ኚ䛺䛧䚹 25䉝/75䠂RH 6 䞃᭶ PTP ໟ ◳ᗘ䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾㡯┠䛿ኚ䛺䛧䚹 2) 䜾䝷䝅䞁䝷䝭䝛䞊䝖⣬➼ໟ䛾Ᏻᐃᛶヨ㦂 19) ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 25䉝/75䠂RH 90 ᪥ 䜾䝷䝅䞁䝷䝭䝛䞊䝖⣬ ◳ᗘ䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾㡯┠䛿ኚ䛺䛧䚹 25䉝/75䠂RH 90 ᪥ 䜾䝷䝅䞁䝷䝭䝛䞊䝖⣬ 䜰䝹䝭䝙䜴䝮⿄ ኚ䛺䛧䚹 40䉝/75䠂RH 90 ᪥ 䜾䝷䝅䞁䝷䝭䝛䞊䝖⣬ ◳ᗘ䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾㡯┠䛿ኚ䛺䛧䚹 3) ↓ໟ䛾Ᏻᐃᛶヨ㦂 20䠅 ಖᏑ᮲௳ ಖᏑᮇ㛫 25䉝/75䠂RH 90 ᪥ 25䉝᭚ග 䠄4,000lux/hr䠅 1,440,000 lux䡡hr 40䉝 90 ᪥ ಖᏑᙧែ 䝥䝷䝇䝏䝑䜽䝅䝱䞊䝺 䠄㛤ᨺ䠅 ㏱᫂䜺䝷䝇⎼ 䠄ᐦᰦ䠅 〓Ⰽ䜺䝷䝇⎼ 䠄ᐦᰦ䠅 8 ⤖ᯝ ◳ᗘ䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾㡯┠䛿ኚ䛺䛧䚹 ኚ䛺䛧䚹 ኚ䛺䛧䚹 (5) ⢊○ᚋ䛾Ᏻᐃᛶヨ㦂 21䠅 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 25䉝/75䠂RH 90 ᪥ 䜾䝷䝅䞁䝷䝭䝛䞊䝖⣬ ኚ䛺䛧䚹 (6) ༙㘄ศᚋ䛾Ᏻᐃᛶヨ㦂 22䠅 ಖᏑ᮲௳ ಖᏑᮇ㛫 ಖᏑᙧែ ⤖ᯝ 25䉝/75%RH 90 ᪥ 䜾䝷䝅䞁䝷䝭䝛䞊䝖⣬ ◳ᗘ䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾㡯┠䛿ኚ䛺䛧䚹 䠑䠊 ㄪ〇ἲཬ䜃⁐ゎᚋ䛾Ᏻᐃᛶ ヱᙜ䛧䛺䛔䚹 䠒䠊 䛸䛾㓄ྜኚ䠄≀⌮Ꮫⓗኚ䠅23䠅 䠘ヨ㦂᪉ἲ䠚 1) 㓄ྜ᪉ἲ䠖䜶䝣䝢䞊OD 㘄 2.5 䜢⢊ᮎ䛸䛧䚸䛣䜜䛻ᑐ㇟⸆䜢ຍ䛘䛶ΰ䛧䚸䜾䝷䝅䞁䝷䝭䝛 䞊䝖⣬䛷ศໟ䛧䛯䚹 2) ಖᏑ᮲௳䠖25Υ/75%RH 3) ಖᏑᮇ㛫䠖33 ᪥㛫 䠘䛸䛾㓄ྜኚヨ㦂⤖ᯝ䠚 㓄ྜ⸆ ⤖ᯝ 䜰䞊䝔䞁ᩓ 1% 䝣䜯䜲䝄䞊 ኚ䛺䛧䚹 䜰䜻䝛䝖䞁⣽⢏ 1% ᪥ᮏఫ〇⸆ ኚ䛺䛧䚹 䜲䞊䝅䞊䞉䝗䝟䞊䝹 㓄ྜ㘄 ༠Ⓨ㓝䜻䝸䞁 7 ᪥┠䜎䛷ኚ䛺䛧䚹 䠄14 ᪥┠䛻ᢞ䛻ᕪ䛧ᨭ䛘䜛⛬ᗘ䛾ሢ䛜⏕䛨䛯䠅 䜹䝞䝃䞊䝹㘄 0.25mg 䝣䜯䜲䝄䞊 ኚ䛺䛧䚹 䝁䝮䝍䞁㘄 100mg 䝜䝞䝹䝔䜱䝇䝣䜯䞊䝬 ኚ䛺䛧䚹 䝅䞁䝯䝖䝺䝹⣽⢏ 10% 䝜䝞䝹䝔䜱䝇䝣䜯䞊䝬 14 ᪥┠䜎䛷ኚ䛺䛧䚹 䠄33 ᪥┠䛻ྵ㔞䛾ⴭ䛧䛔పୗ䛜ㄆ䜑䜙䜜䛯䠅 䝗䝟䞊䝹⣽⢏ 99.5䠂 ༠Ⓨ㓝䜻䝸䞁 ኚ䛺䛧䚹 䝗䝟䝇䝖䞁ᩓ 98.5% ➨୍୕ඹ ኚ䛺䛧䚹 䝗䝥䝇⣽⢏ 20% ᪥ᮏఫ〇⸆ ኚ䛺䛧䚹 䝗䝭䞁㘄 0.4 ᪥ᮏ䝧䞊䝸䞁䜺䞊 䜲䞁䝀䝹䝝䜲䝮 14 ᪥┠䜎䛷ኚ䛺䛧䚹 䠄33 ᪥┠䛻ᢞ䛻ᕪ䛧ᨭ䛘䜛⛬ᗘ䛾ሢ䛜⏕䛨䛯䠅 䝛䜸䝗䝟䝌䞊䝹 㓄ྜ㘄 ➨୍୕ඹ 14 ᪥┠䜎䛷ኚ䛺䛧䚹 䠄33 ᪥┠䛻ᢞ䛻ᕪ䛧ᨭ䛘䜛⛬ᗘ䛾ሢ䛜⏕䛨䛯䠅 9 㓄ྜ⸆ ⤖ᯝ 䝟䞊䝻䝕䝹㘄 2.5mg 䝜䝞䝹䝔䜱䝇䝣䜯䞊䝬 ኚ䛺䛧䚹 䝡䞉䝅䝣䝻䞊䝹㘄 0.125mg ᪥ᮏ䝧䞊䝸䞁䜺䞊 䜲䞁䝀䝹䝝䜲䝮 ኚ䛺䛧䚹 䝨䝹䝂䝸䞁㢛⢏ 0.025% ᪥་ᕤ ኚ䛺䛧䚹 䝬䝗䝟䞊㓄ྜ㘄 ୰እ〇⸆ 14 ᪥┠䜎䛷ኚ䛺䛧䚹 䠄33 ᪥┠䛻ᢞ䛻ᕪ䛧ᨭ䛘䜛⛬ᗘ䛾ሢ䛜⏕䛨䛯䠅 䝯䝛䝅䝑䝖㘄 250 MSD ኚ䛺䛧䚹 䝺䜻䝑䝥㘄 0.25mg 䜾䝷䜽䝋䞉䝇䝭䝇䜽䝷䜲䞁 ኚ䛺䛧䚹 䠓䠊 ⁐ฟᛶ ᪥ᮏ⸆ᒁ᪉䛂⁐ฟヨ㦂ἲ 䝟䝗䝹ἲ䛃䛻䜘䜚ヨ㦂䜢⾜䛖䛸䛝䚸䛣䜜䛻㐺ྜ䛩䜛䚹 ᮲௳䠖 ᅇ㌿ᩘ 50rpm ヨ㦂ᾮ Ỉ 䠘༙㘄䛾⁐ฟᛶ䠚22䠅 ㏻ᖖ䛾㘄䠄䜶䝣䝢䞊OD 㘄 2.5䠅䛸༙ษᶵ䛷ศ䛧䛯㘄䛻䛴䛔䛶⁐ฟヨ㦂䜢⾜䛳䛯⤖ᯝ䚸୧〇 䛾⁐ฟᣲື䛿ྠ➼䛷䛒䛳䛯䚹 ᶆ‽〇 䠖㏻ᖖ䛾㘄 ヨ㦂〇 䠖༙ษᶵ䛷ศ䛧䛯㘄䠄1 㘄ศ䠅 [⁐ฟᣲື䛾ྠ➼ᛶุᐃᇶ‽] ᶆ‽〇䛾ᖹᆒ⁐ฟ⋡䛜⣙ 60䠂ཬ䜃 85䠂䛸䛺䜛㐺ᙜ䛺 2 Ⅼ䛻䛚䛔䛶䚸ヨ㦂〇䛾ᖹᆒ⁐ฟ ⋡䛜ᶆ‽〇䛾ᖹᆒ⁐ฟ⋡ ±10%䛾⠊ᅖ䛻䛒䜛䛸䛝ྠ➼䛸ุᐃ䛩䜛䚹 [ヨ㦂⤖ᯝ] 100 80 ᖹ ᆒ ⁐ ฟ ⋡ ( % 60 : ᶆ‽〇㸦㏻ᖖࡢ㘄㸧 : ヨ㦂〇㸦ศࡋࡓ㘄㸧 40 ) 20 0 0 10 20 30 40 㛫㸦ศ㸧 10 50 60 䠔䠊 ⏕≀Ꮫⓗヨ㦂ἲ ヱᙜ䛧䛺䛔䚹 䠕䠊 〇୰䛾᭷ຠᡂศ䛾☜ㄆヨ㦂ἲ 䝥䝻䝢䝙䝹ᇶ䛾࿊Ⰽᛂ䛻䜘䜚☜ㄆ䛩䜛䜋䛛ⷧᒙ䜽䝻䝬䝖䜾䝷䝣䜱䞊ཬ䜃ᾮయ䜽䝻䝬䝖䜾䝷䝣䜱䞊䛻 䜘䜚䝉䝺䜼䝸䞁ሷ㓟ሷᶆ‽ရ䛸ẚ㍑䛩䜛䚹 10䠊 〇୰䛾᭷ຠᡂศ䛾ᐃ㔞ἲ ᪥ᮏ⸆ᒁ᪉䞉୍⯡ヨ㦂ἲ䡞ᾮయ䜽䝻䝬䝖䜾䝷䝣䜱䞊䡟䛻䜘䜚ᐃ㔞䛩䜛䚹 11䠊 ຊ౯ ᮏ䛿ຊ౯⾲♧䛻ヱᙜ䛧䛺䛔䚹 12䠊 ΰධ䛩䜛ྍ⬟ᛶ䛾䛒䜛ዃ㞧≀ ヱᙜ㈨ᩱ䛺䛧䚹 13䠊 ὀព䛜ᚲせ䛺ᐜჾ䞉እほ䛜≉Ṧ䛺ᐜჾ䛻㛵䛩䜛ሗ ≉䛻䛺䛧䚹 14䠊 䛭䛾 ≉䛻䛺䛧䚹 11 䊤䠊⒪䛻㛵䛩䜛㡯┠ 䠍䠊 ຠ⬟ཪ䛿ຠᯝ 䝟䞊䜻䞁䝋䞁䠄䝺䝪䝗䝟ྵ᭷〇䜢ే⏝䛩䜛ሙྜ䠖Yahr 㔜ᗘ䝇䝔䞊䝆䊠䡚䊣䚸䝺䝪䝗䝟ྵ᭷〇 䜢ే⏝䛧䛺䛔ሙྜ䠖Yahr 㔜ᗘ䝇䝔䞊䝆䊠䡚䊢䠅 䠎䠊 ⏝ἲཬ䜃⏝㔞 䝺䝪䝗䝟ྵ᭷〇䜢ే⏝䛩䜛ሙྜ䠖 ㏻ᖖ䚸ᡂே䛻䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛧䛶 1 ᪥ 1 ᅇ 2.5mg 䜢ᮅ㣗ᚋ᭹⏝䛛䜙ጞ䜑䚸2 㐌䛤䛸䛻 1 ᪥ 㔞䛸䛧䛶 2.5mg 䛪䛴ቑ㔞䛧䚸᭱㐺ᢞ㔞䜢ᐃ䜑䛶䚸⥔ᣢ㔞䛸䛩䜛䠄ᶆ‽⥔ᣢ㔞 1 ᪥ 7.5mg䠅䚹1 ᪥㔞䛜䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛧䛶 5.0mg ௨ୖ䛾ሙྜ䛿ᮅ㣗ཬ䜃㣗ᚋ䛻ศ᭹䛩䜛 䈜䚹䛯䛰䛧䚸 7.5mg 䛾ሙྜ䛿ᮅ㣗ᚋ 5.0mg ཬ䜃㣗ᚋ 2.5mg 䜢᭹⏝䛩䜛䚹 䛺䛚䚸ᖺ㱋䚸≧䛻ᛂ䛨䛶㐺ᐅቑῶ䛩䜛䛜 1 ᪥ 10mg 䜢㉸䛘䛺䛔䛣䛸䛸䛩䜛䚹 䝺䝪䝗䝟ྵ᭷〇䜢ే⏝䛧䛺䛔ሙྜ䠖 ㏻ᖖ䚸ᡂே䛻䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛧䛶 1 ᪥ 1 ᅇ 2.5mg 䜢ᮅ㣗ᚋ᭹⏝䛛䜙ጞ䜑䚸2 㐌䛤䛸䛻 1 ᪥ 㔞䛸䛧䛶 2.5mg 䛪䛴ቑ㔞䛧䚸1 ᪥ 10mg 䛸䛩䜛䚹1 ᪥㔞䛜䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛧䛶 5.0mg ௨ୖ䛾 ሙྜ䛿ᮅ㣗ཬ䜃㣗ᚋ䛻ศ᭹䛩䜛 䈜 䚹䛯䛰䛧䚸7.5mg 䛾ሙྜ䛿ᮅ㣗ᚋ 5.0mg ཬ䜃㣗ᚋ 2.5mg 䜢᭹⏝䛩䜛䚹 䛺䛚䚸ᖺ㱋䚸≧䛻ᛂ䛨䛶㐺ᐅቑῶ䛩䜛䛜 1 ᪥ 10mg 䜢㉸䛘䛺䛔䛣䛸䛸䛩䜛䚹 䈜 ᢞ㛫㝸䛻䛴䛔䛶䛿䚸䝉䝺䜼䝸䞁ሷ㓟ሷ䛿ㅖእᅜ䛻䛚䛔䛶䜒ᮅ㣗ཬ䜃㣗ᚋ䛻ศ᭹䛩䜛⏝ ἲ䛜᥇⏝䛥䜜䛶䛔䜛䛣䛸䚸䜎䛯ㅖእᅜ䛷䛾⏝⤒㦂䛛䜙╀䛾స⏝䛜ሗ࿌䛥䜜䛶䛔䜛䛣䛸䜢 ⪃៖䛧䚸5.0mg ௨ୖ䛾ሙྜ䛿ᮅ㣗ཬ䜃㣗ᚋ䛻ศ᭹䛩䜛䛣䛸䛸䛧䛯䚹 䠘⏝ἲ䞉⏝㔞䛻㛵㐃䛩䜛⏝ୖ䛾ὀព䠚 (1) 䝺䝪䝗䝟ྵ᭷〇ᢞ୰䛾ᝈ⪅䛻ᮏ䛾ᢞ䜢㛤ጞ䛩䜛ሙྜ䚸ཬ䜃ᮏᢞ୰䛾ᝈ⪅䛻 䝺䝪䝗䝟ྵ᭷〇䛾ᢞ䜢㛤ጞ䛩䜛ሙྜ䛻䛿䚸䝺䝪䝗䝟ྵ᭷〇䛸ᮏ䛾ే⏝䛻䜘䜚䝺䝪䝗 䝟䛾స⏝䛜ቑᙉ䛥䜜䜛䛣䛸䛜䛒䜛䛾䛷䚸ほᐹ䜢༑ศ䛻⾜䛔ៅ㔜䛻⥔ᣢ㔞䜢Ỵᐃ䛩䜛䛣䛸䚹 ⥔ᣢ㔞ᢞᚋ䚸䝺䝪䝗䝟䛸ᮏ䛸䛾ే⏝ຠᯝ䛸ᛮ䜟䜜䜛㝶ព㐠ື䚸ᗁぬ䚸ዶ➼䛜䛒䜙䜟 䜜䛯ሙྜ䛻䛿䚸ᮏཪ䛿䝺䝪䝗䝟䛾ῶ㔞➼㐺ษ䛻ฎ⨨䜢⾜䛖䛣䛸䚹䛺䛚䚸ᮏཪ䛿䝺䝪䝗䝟 䛾ῶ㔞䜢⾜䛖㝿䛻䛿䚸ᮏ䛾 MAO-B 㜼ᐖస⏝䛜㛗ᮇ㛫ᣢ⥆䛧䛶ຠᯝ䛾ῶᙅ䛻㛫䜢せ䛩 䜛䛣䛸䜒⪃៖䛩䜛䛣䛸䚹䠄䛂⸆≀ືែ䛃䛾㡯ཧ↷䠅 (2) ᮏ䛿ཱྀ⭍ෆ䛷ᔂቯ䛩䜛䛜䚸ཱྀ⭍⢓⭷䛛䜙䛾྾䜢┠ⓗ䛸䛧䛺䛔䛯䜑䚸ၚᾮཪ䛿Ỉ䛷㣧䜏 ㎸䜐䛣䛸䚹䠄䛂㐺⏝ୖ䛾ὀព䛃䛾㡯ཧ↷䠅 䠏䠊 ⮫ᗋᡂ⦼ 䜶䝣䝢䞊㘄 2.5 ཬ䜃䜶䝣䝢䞊OD 㘄 2.5 䛾㔜┣᳨ẚ㍑ヨ㦂䜢ྵ䜐⮫ᗋヨ㦂䛾ᡂ⦼䛿ḟ䛾䛸䛚䜚 䛷䛒䜛䚹 (1) ⮫ᗋ䝕䞊䝍䝟䝑䜿䞊䝆 ヱᙜ䛧䛺䛔䚹 12 (2) ⮫ᗋຠᯝ 1) 㔜┣᳨ẚ㍑ヨ㦂䜢ྵ䜐䝺䝪䝗䝟ྵ᭷〇ే⏝䛾䝟䞊䜻䞁䝋䞁䛾ᨵၿ⋡䛿䚸୰➼ᗘᨵၿ ௨ୖ 32.1䠂䠄90/280䠅䚸㍍ᗘᨵၿ௨ୖ 69.3䠂䠄194/280䠅䛷䛒䛳䛯䚹䜎䛯㔜┣᳨ẚ㍑ヨ㦂 䛻䜘䛳䛶䝺䝪䝗䝟ྵ᭷〇ే⏝䛾䝟䞊䜻䞁䝋䞁䛻ᑐ䛩䜛ᮏ䛾᭷⏝ᛶ䛜ㄆ䜑䜙䜜䛶䛔䜛 䠄䜶䝣䝢䞊㘄 2.5䠅7䡚10)䚹 2) 䝺䝪䝗䝟ྵ᭷〇ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯㛗ᮇᢞヨ㦂䛻䛚䛡䜛ᨵၿ⋡䛿 6 䞃᭶䛷䛿୰➼ᗘᨵၿ௨ୖ 49.3䠂䠄37/75䠅䚸㍍ᗘᨵၿ௨ୖ 85.3䠂䠄64/75䠅䚸12 䞃᭶䛷䛿 ୰➼ᗘᨵၿ௨ୖ 51.7䠂䠄31/60䠅䚸㍍ᗘᨵၿ௨ୖ 85.0䠂䠄51/60䠅䛷䛒䛳䛯䚹䜎䛯䚸䝺䝪䝗䝟ྵ ᭷〇ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅ 32 䜢ᑐ㇟䛻䚸ᮏ䛸䝺䝪䝗䝟ྵ᭷〇䛸䛾ే⏝䛷䚸1 ᖺ 㛫ᢞ䛧䛯ヨ㦂䛻䜘䜛䛸䚸6 䞃᭶䛷䛿 72.3mg/᪥䠄14.7䠂䠅䚸12 䞃᭶䛷䛿 61.6mg/᪥ 䠄12.5䠂䠅䛾䝺䝪䝗䝟ᢞ㔞䛾ῶ㔞䛜ྍ⬟䛷䛒䛳䛯䠄䜶䝣䝢䞊㘄 2.5䠅24䡚26)䚹 3) 䝺䝪䝗䝟ྵ᭷〇㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯➨䊢┦ヨ㦂䛻䛚䛡䜛᪥ᮏㄒ∧ UPDRS part䊠䚸䊡䚸䊢ྜィ䝇䝁䜰䛾䝧䞊䝇䝷䜲䞁䛛䜙䛾ኚ㔞䜢ᮏ༢⊂⩌䠄139 䠅䛸䝥 䝷䝉䝪⩌䠄140 䠅䛷ẚ㍑䛧䛯⤖ᯝ䚸᭷ព䛺ᕪ䛜ㄆ䜑䜙䜜䛯䠄䜶䝣䝢䞊OD 㘄 2.5 ຠ⬟㏣ຍᢎ ㄆ䠅15䠅䚹 ኚ㔞 ᪥ᮏㄒ∧ UPDRS Part 䊠䚸 䊡䚸䊢䛾ྜィ䝇䝁䜰 ᢞ⩌ ᮏ༢⊂⩌ 䝥䝷䝉䝪⩌ a) ᩘ 139 140 䝧䞊䝇䝷䜲䞁 ᭱⤊ホ౯ 䝧䞊䝇 䝷䜲䞁䛛䜙䛾 ኚ㔞 26.5 ± 11.2 20.2 ± 13.0 䌦6.3 ± 0.6 26.6 ± 11.5 b,c䠅 23.4 ± 13.6 䝥䝷䝉䝪⩌䛸䛾ẚ㍑ ⩌㛫ᕪ [95%ಙ㢗༊㛫] p್ 䌦3.1 ± 0.9 [䌦4.9䡚䌦1.4] 0.0005 䌦3.1 ± 0.6 a) ᖹᆒ್㼼ᶆ‽೫ᕪ b) ᭱ᑠᖹᆒ್䠄LSMEAN䠅㼼ᶆ‽ㄗᕪ c) 䝧䞊䝇䝷䜲䞁䛾᪥ᮏㄒ∧ UPDRS part䊠䚸䊡䚸䊢䛾ྜィ䝇䝁䜰䜢ඹኚ㔞䛸䛧䛯ඹศᩓศᯒ 4) 䝺䝪䝗䝟ྵ᭷〇㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅ 131 䜢ᑐ㇟䛸䛧䛯 56 㐌㛫ᢞ䛾㛗ᮇヨ 㦂䛻䛚䛔䛶䚸᪥ᮏㄒ∧ UPDRS part䊠䚸䊡䚸䊢ྜィ䝇䝁䜰䛾䝧䞊䝇䝷䜲䞁䛛䜙䛾ኚ㔞 䠄LSMEAN䠅䛿䚸ᢞ 4 㐌ᚋ䛷䌦2.6䚸ᢞ 20 㐌ᚋ䛷䌦5.6䚸ᢞ 56 㐌ᚋ䛷䌦2.8 䛷䛒䜚䚸 㛗ᮇᢞ䜒ຠᯝ䛜⥔ᣢ䛥䜜䛯䠄䜶䝣䝢䞊OD 㘄 2.5 ຠ⬟㏣ຍᢎㄆ䠅16䠅䚹 (3) ⮫ᗋ⸆⌮ヨ㦂䠖ᚸᐜᛶヨ㦂 ᗣᡂே 9 䛻ᑐ䛧䛶䚸䜶䝣䝢䞊㘄 2.5 䜢 2.5䡚15.0mg ὀ)䜢༢ᅇᢞ䛧䛯⤖ᯝ䚸⬻Ἴ᳨ᰝ䛷 2 䛻୍㐣ᛶ㧗ᖜᚎἼ䛜䜏䜙䜜䛯䛜䚸䜶䝣䝢䞊㘄 2.5 䛸䛾ᅉᯝ㛵ಀ䛿᫂䛷䛒䛳䛯䚹䛥䜙䛻䚸⮬ ぬ≧䛸䛧䛶䚸㢌③➼䛾㍍ᚤ䛷୍㐣ᛶ䛾≧䛜䜏䜙䜜䛯䛜䚸≉䛻ၥ㢟䛸䛺䜛䜒䛾䛷䛿䛺䛛䛳䛯䚹 13 䜎䛯䚸ᗣᡂே 6 䛻ᑐ䛧䛶䚸5.0mg 䜒䛧䛟䛿 10.0mg 䜢 1 ᪥ 1 ᅇ 7 ᪥㛫ᢞ䛧䛯⤖ᯝ䚸㢌䛜㔜 䛔➼䛾≧䛜䜏䜙䜜䛯䛜䚸≉䛻ၥ㢟䛸䛺䜛䜒䛾䛷䛿䛺䛛䛳䛯 27)䚹 ὀ䠅䜶䝣䝢䞊㘄 2.5 䛾ᢎㄆ䛥䜜䛯᭱ᢞ㔞䛿 10mg/᪥䛷䛒䜛䚹 (4) ᥈⣴ⓗヨ㦂䠖⏝㔞ᛂ᥈⣴ヨ㦂 䝟䞊䜻䞁䝋䞁ᝈ⪅ 95 䜢ᑐ㇟䛻ึᮇᢞ㔞䜢 2.5mg/᪥䚸䛭䛾ᚋ 10.0mg/᪥䜎䛷ቑྍ⬟ 䠄᭦䛻ຠᯝ䛜ᮇᚅ䛷䛝䜛ሙྜ䛾䜏䚸15.0mg/᪥䜎䛷ቑྍ⬟ὀ䠅䠅䛸䛧䚸ホ౯ᮇ㛫 12 㐌㛫䛸䛧䛯ヨ 㦂䛾⤖ᯝ䚸䜶䝣䝢䞊㘄 2.5 䛾⮳㐺⏝㔞䛿 5.0䡚10.0mg 䛷䛒䜛䛸ุ᩿䛥䜜䛯 8,9)䚹 ὀ䠅䜶䝣䝢䞊㘄 2.5 䛾ᢎㄆ䛥䜜䛯᭱ᢞ㔞䛿 10mg/᪥䛷䛒䜛䚹 (5) ᳨ドⓗヨ㦂 1) ↓సⅭ୪⾜⏝㔞ᛂヨ㦂 ヱᙜ㈨ᩱ䛺䛧䚹 2) ẚ㍑ヨ㦂 䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛻ึᮇᢞ㔞䜢 2.5mg/᪥䚸䛭䛾ᚋ 5.0䡚10.0mg 䜎䛷ቑྍ⬟䛸 䛧䚸16 㐌㛫䛾ホ౯ᮇ㛫䛷㔜┣᳨ẚ㍑ヨ㦂䜢ᐇ䛧䛯⤖ᯝ䚸䜶䝣䝢䞊㘄 2.5 䛾᭷ຠᛶ䛜ㄆ 䜑䜙䜜䛯䚹䛺䛚䚸ᑐ↷⸆䛿䝥䝷䝉䝪䜢⏝䛧䛯 10)䚹 3) Ᏻᛶヨ㦂 䜶䝣䝢䞊㘄 2.5 䛾➨䊡┦ヨ㦂䜘䜚⛣⾜䛧䛯䝟䞊䜻䞁䝋䞁ᝈ⪅ 47 䜢ᑐ㇟䛻䚸1 ᪥ᢞ㔞 2.5䡚15.0mg ὀ䠅䚸ホ౯ᮇ㛫䜢 5 ᖺ䛸䛧䛯㛗ᮇヨ㦂䛾⤖ᯝ䚸䜶䝣䝢䞊㘄 2.5 䛾㛗ᮇ⏝䛻䜘䜛 ᭷⏝ᛶ䛜ㄆ䜑䜙䜜䛯 28)䚹 ὀ䠅䜶䝣䝢䞊㘄 2.5 䛾ᢎㄆ䛥䜜䛯᭱ᢞ㔞䛿 10mg/᪥䛷䛒䜛䚹 4) ᝈ⪅䞉ែูヨ㦂 ヱᙜ㈨ᩱ䛺䛧 (6) ⒪ⓗ⏝ 1) ⏝ᡂ⦼ㄪᰝ䞉≉ᐃ⏝ᡂ⦼ㄪᰝ䠄≉ูㄪᰝ䠅䞉〇㐀㈍ᚋ⮫ᗋヨ㦂䠄ᕷ㈍ᚋ⮫ᗋヨ㦂䠅 ⏝ᡂ⦼ㄪᰝ䠄䜶䝣䝢䞊㘄 2.5䠅䠖 1998 ᖺ 7 ᭶ 3 ᪥䛾ᢎㄆ䛛䜙 2004 ᖺ 7 ᭶ 2 ᪥䜎䛷䛾 6 ᖺ㛫䛷䚸ᅜ 490 タ䛛䜙 4,717 䜢㞟䛧䛯䚹䛭䛾⤖ᯝ䚸᭷ຠᛶゎᯒᑐ㇟䛿 4,328 䚸Ᏻᛶゎᯒᑐ㇟䛿 4,692 䛷䛒䛳䛯䚹 䠷᭷ຠᛶ䠹 ᭷ຠᛶ㞟ィᑐ㇟ 4,328 䛻䛴䛔䛶䚸せホ౯㡯┠䛷䛒䜛 UPDRS ᢤ⢋ 6 㡯┠䛾ྜ ィⅬᩘཬ䜃 Yahr 㔜ᗘ䜢ᣦᶆ䛸䛧䛯ᨵၿ⋡䛿䚸䛭䜜䛮䜜 65.2䠂䚸18.8䠂䛷䛒䜚䚸యⓗ 䛺ホ౯䛷䛒䜛䛂ᢸᙜ་ᖌ䛾༳㇟䛃䜢ᣦᶆ䛸䛧䛯᭷ຠ⋡䛿 73.6䠂䛷䛒䛳䛯䚹 䜎䛯䚸UPDRS ᢤ⢋ 6 㡯┠䠄䛂Ᏻ㟼ᡓ䛃䚸䛂ᅛ⦰䛃䚸䛂Ṍ⾜䛃䚸䛂ጼໃ䛾Ᏻᐃᛶ䛃䚸䛂ືస⦆ ៏䛸㐠ືῶᑡ䛃䚸䛂㉳䛝䛶䛔䜛㛫䛾ఱ䠂䛜䜸䝣ᮇ㛫䛛䠛䛃䠅䛾≧䛻䛴䛔䛶䚸≧䜢᭷䛩䜛 14 䛾ᨵၿ⋡䛿䚸䛂Ᏻ㟼ᡓ䛃䛜 35.5䠂䚸䛂ᅛ⦰䛃䛜 32.9䠂䚸䛂Ṍ⾜䛃䛜 32.5䠂䚸䛂ጼໃ䛾 Ᏻᐃᛶ䛃䛜 26.9䠂䚸䛂ືస⦆៏䛸㐠ືῶᑡ䛃䛜 36.1䠂䚸䛂㉳䛝䛶䛔䜛㛫䛾ఱ䠂䛜䜸䝣ᮇ㛫 䛛䠛䛃䛜 39.7䠂䛷䛒䛳䛯䚹 䠷Ᏻᛶ䠹 Ᏻᛶゎᯒᑐ㇟ 4,692 䛾స⏝Ⓨ⌧䛿 957 䠄20.4䠂䠅䛷䛒䜚䚸స⏝Ⓨ⌧ ௳ᩘ䛿 1,266 ௳䛷䛒䛳䛯䚹䛺స⏝䛿ᗁぬ䠄4.8䠂䠅䚸ᝏᚰ䠄3.1䠂䠅䚸䝆䝇䜻䝛䝆䜰 䠄2.3䠂䠅䚸䜑䜎䛔䠄1.6䠂䠅䚸㣗ḧ䠄1.0䠂䠅䛷䛒䛳䛯䚹 䠷䝺䝪䝗䝟ῶ㔞䛻䜘䜛స⏝䛾㍍ῶຠᯝ䠹 స⏝䛾ฎ⨨䛸䛧䛶䝺䝪䝗䝟ῶ㔞䜢ᐇ䛧䛯䠄111 䠅䜢ᑐ㇟䛻స⏝㍍ῶຠᯝ䜢ㄪ ᰝ䛧䛯䚹䛭䛾⤖ᯝ䚸䝺䝪䝗䝟ῶ㔞䜢ྵ䜐ฎ⨨䛻䜘䜚 71 䠄64.0䠂䠅䛷స⏝䛾㍍ῶ䛜䜏䜙䜜䚸 ᮍᅇ䜢ྵ䜑 87 䠄78.6䠂䠅䛷䜶䝣䝢䞊㘄 2.5 䛾ᢞ䛜⥅⥆䛥䜜䛯䚹㍍ῶ䛜䜏䜙䜜䛯䛺 స⏝䛿䚸ᗁぬ䚸䝆䝇䜻䝛䝆䜰䚸ዶ䚸ᝏᚰ䚸䛫䜣ዶ䛷䛒䛳䛯䚹 ≉ูㄪᰝ䠄䜶䝣䝢䞊㘄 2.5䠅䠖 ⥅⥆ㄪᰝ ᢎㄆ᮲௳䛻ᇶ䛵䛝䚸㛗ᮇᢞ䛻䜘䜛᭷ຠᛶ䚸Ᏻᛶ䚸⥅⥆ᢞ䛾ྍ⬟ᛶ䜢ㄪᰝ䛧䚸2,614 䛾䜢㞟䛧䛯䚹䛭䛾⤖ᯝ䚸᭷ຠᛶゎᯒᑐ㇟䛿 2,410 䚸Ᏻᛶゎᯒᑐ㇟ 䛿 2,596 䛷䛒䛳䛯䚹䜎䛯䚸⥅⥆ᢞ䛾ྍ⬟ᛶ䛿Ᏻᛶゎᯒᑐ㇟䛾 2,596 䜢ᑐ㇟ 䛸䛧䛯䚹 䠷᭷ຠᛶ䠹 ᭷ຠᛶゎᯒᑐ㇟ 2,410 䛻䛴䛔䛶䚸యⓗ䛺ホ౯䛷䛒䜛䛂ᢸᙜ་ᖌ䛾༳㇟䛃䜢ᣦᶆ 䛸䛧䛯㛗ᮇᢞ䛷䛾᭷ຠ⋡䛿 70.3䠂䛷䛒䛳䛯䚹 䠷Ᏻᛶ䠹 Ᏻᛶゎᯒᑐ㇟ 2,596 䛾స⏝Ⓨ⌧䛿 485 䠄18.7䠂䠅䛷䛒䛳䛯䚹 䠷⥅⥆ᢞ䛾ྍ⬟ᛶ䠹 ᑐ㇟ 2,596 䛻䛴䛔䛶䚸୰Ṇ䞉⬺ⴠཬ䜃ㄪᰝ⤊䛻䛚䛡䜛䜶䝣䝢䞊㘄 2.5 䛾ᢞ ⥅⥆䛾ྍྰ䜢ㄪᰝ䛧䛯⤖ᯝ䚸79.9䠂䛾䛷ᢞ⥅⥆䛜ྍ⬟䛸ホ౯䛥䜜䛯䚹 ணᚋㄪᰝ 1995 ᖺ䛻䛂ⱥᅜ䛾⮫ᗋヨ㦂䛻䛚䛔䛶䚸䝺䝪䝗䝟䞉䝉䝺䜼䝸䞁ే⏝⩌䛾Ṛஸ⋡䛜䝺䝪䝗䝟༢ ⊂⩌䛾Ṛஸ⋡䜘䜚ከ䛛䛳䛯䚹䜎䛯Ṛஸཎᅉ䛸䛧䛶⾑ᛶᚰᝈ䚸⬻⾑ᝈ䚸ᚰ⾑⟶㞀ᐖ 䛜ከ䛛䛳䛯䛃䛸䛾ㄽᩥ 29) 䛜බ⾲䛥䜜䛯䛣䛸䜢䛖䛡䚸䛂ணᚋ䛻㛵䛩䜛䝕䞊䝍䜢㞟䛩䜛䛣䛸䛃䛸䛾 ᢎㄆ᮲௳䛜䛥䜜䛯䚹 ᮏㄪᰝ䛷䛿䜶䝣䝢䞊㘄 2.5 䛾ᢞ䜢⾜䛳䛯 3,134 䜢ணᚋㄪᰝ䛾ᑐ㇟䛸䛧䛶䚸᥎ᐃṚஸ⋡ 䛾⟬ฟཬ䜃Ṛஸཎᅉ䛾☜ㄆ䜢⾜䛳䛯䚹 䠷᥎ᐃṚஸ⋡䠹 ணᚋㄪᰝᑐ㇟ 3,134 䛻䛚䛔䛶䚸290 䛾Ṛஸ䠄䜶䝣䝢䞊㘄 2.5 䛸䛾ᅉᯝ㛵ಀ䛺䛧 䜢ྵ䜐䠅䛜ㄆ䜑䜙䜜䚸䛭䛾᥎ᐃṚஸ⋡䠄ேᖺἲ䠖1 ᖺ㛫䚸1,000 ே䛒䛯䜚䛾᥎ᐃṚஸᩘ䠅䛿 30.0 ே/ᖺ䞉1,000 ே䛷䛒䛳䛯䚹䛣䛾⤖ᯝ䛿䚸1995 ᖺ䛻බ⾲䛥䜜䛯ㄽᩥ䛾Ṛஸ⋡䠄䝺䝪䝗 䝟䞉䝉䝺䜼䝸䞁ే⏝⩌䠖50.7 ே/ᖺ䞉1,000 ே䠅䜘䜚ప䛟䚸䛥䜙䛻䝺䝪䝗䝟༢⊂⩌䛾Ṛஸ⋡ 15 䠄32.1 ே/ᖺ䞉1,000 ே䠅䜘䜚䜒ప䛛䛳䛯䚹 䠷Ṛஸཎᅉ䠹 Ṛஸ 290 䛾䛺Ṛஸཎᅉ䛿⫵⅖䚸ᝏᛶ⭘⒆➼䛷䛒䜚䚸๓㏙䛾ㄽᩥ 29) 䛷ሗ࿌䛥䜜 䛯⾑ᛶᚰᝈ䚸⬻⾑䚸ᚰ⾑⟶㞀ᐖ䛷䛿䛺䛛䛳䛯䚹 㧗㱋⪅䛻ᑐ䛩䜛ㄪᰝ ⏝ᡂ⦼ㄪᰝ䛾Ᏻᛶゎᯒᑐ㇟ 4,692 䜢ᑐ㇟䛸䛧䛶㞟ィ䛧䛯䚹 65 ṓ௨ୖ䛾䛻䛚䛡䜛స⏝Ⓨ⌧⋡䛿 21.9䠂䠄621/2,832䠅䛷䛒䜚䚸65 ṓᮍ‶䛾 䛻䛚䛡䜛స⏝Ⓨ⌧⋡䛿 18.1䠂䠄336/1,860䠅䛷䛒䛳䛯䚹≧ู䛷䛿䚸65 ṓ௨ୖ䛾䛷 㣗ḧ䚸䛫䜣ዶ䚸ᗁぬ䚸㉳❧ᛶప⾑ᅽ䚸ྤ䚸Ṍ⾜␗ᖖ䛜ከ䛟ㄆ䜑䜙䜜䛯䚹 䜎䛯䚸75 ṓ௨ୖ䛾䛻䛚䛡䜛స⏝Ⓨ⌧⋡䛿 22.0䠂䠄199/905䠅䛷䛒䜚䚸75 ṓᮍ‶䛾 䛻䛚䛡䜛స⏝Ⓨ⌧⋡䛿 20.0䠂䠄758/3,787䠅䛷䛒䛳䛯䚹≧ู䛷䛿䚸75 ṓ௨ୖ䛾 䛷㣗ḧ䚸ᗁぬ䚸㉳❧ᛶప⾑ᅽ䚸ᝏᚰ䚸Ṍ⾜ᅔ㞴䛜ከ䛟ㄆ䜑䜙䜜䛯䚹 䛭䛾䛾ㄪᰝ ⫢ᶵ⬟㞀ᐖ䜢᭷䛩䜛ᝈ⪅䚸⭈ᶵ⬟㞀ᐖ䜢᭷䛩䜛ᝈ⪅䚸⢭⚄ᝈ䜢᪤ 䛒䜛䛔䛿ྜే䛩䜛 ᝈ⪅䛻ᑐ䛩䜛ㄪᰝ䜢ᐇ䛧䛯䛜䚸ၥ㢟䛸䛺䜛㡯䛿ㄆ䜑䜙䜜䛶䛔䛺䛔䚹 䛺䛚䚸ᑠඣ䚸ዷ⏘፬䛿ヱᙜ䛜䛺䛛䛳䛯䚹 2) ᢎㄆ᮲௳䛸䛧䛶ᐇணᐃ䛾ෆᐜཪ䛿ᐇ䛧䛯ヨ㦂䛾ᴫせ ヱᙜ䛧䛺䛔䚹 䠘ཧ⪃䠖䜶䝣䝢䞊㘄 2.5䠚 䜶䝣䝢䞊㘄 2.5 䛿ᢎㄆ᮲௳䛸䛧䛶䚸䛂ᚋ䚸ᑂᰝᮇ㛫⤊䜎䛷䛿䚸ᅜෆ䛷⏝䛥䜜䜛䛻 㛵䛧䛶䛿䚸ྍ⬟䛺㝈䜚ᢞ䜢ᕷ㈍ᚋㄪᰝ䛾ᑐ㇟䛸䛧䚸ᮏ⸆䛾㛗ᮇᢞ䛻䜘䜛᭷ຠᛶ䚸 Ᏻᛶ䚸⥅⥆ᢞ䛾ྍ⬟ᛶ䚸ணᚋ䛻㛵䛧䛶䝕䞊䝍䛾㞟䜢⾜䛔䚸ᑂᰝ䛾㈨ᩱ䛸䛧䛶ᥦฟ 䛩䜛䛣䛸䛃䛜䛥䜜䚸ᕷ㈍ᚋㄪᰝ䜢ᐇ䛧䛯䚹䛂1) ⏝ᡂ⦼ㄪᰝ䞉≉ᐃ⏝ᡂ⦼ㄪᰝ䠄≉ู ㄪᰝ䠅䞉〇㐀㈍ᚋ⮫ᗋヨ㦂䠄ᕷ㈍ᚋ⮫ᗋヨ㦂䠅䛃䛾㡯䜢ཧ↷䚹 16 䊥䠊⸆ຠ⸆⌮䛻㛵䛩䜛㡯┠㻌 䠍䠊 ⸆⌮Ꮫⓗ䛻㛵㐃䛒䜛ྜ≀ཪ䛿ྜ≀⩌ MAO 㜼ᐖ䠄safrazine䚸nialamide䚸phenelzine ➼䠅 䠎䠊 ⸆⌮స⏝ (1) స⏝㒊䞉స⏝ᶵᗎ MAO-B䠄B ᆺ䝰䝜䜰䝭䞁㓟㓝⣲䠅䛾㑅ᢥⓗ㜼ᐖ䛷䛒䜛ᮏ䛿䚸䝗䝟䝭䞁䛜ῶᑡ䛧䛶䛔䜛䝟䞊䜻 䞁䝋䞁ᝈ⪅䛾⬻ෆ MAO-B 䜢㜼ᐖ䛧䛶䚸䝅䝘䝥䝇㛫㝽䛾䝗䝟䝭䞁㔞䛾ῶᑡ䜢ᢚไ䛩䜛䚹䜎䛯䚸䝅 䝘䝥䝇䜈䛾䝗䝟䝭䞁䛾ྲྀ䜚㎸䜏㜼ᐖస⏝䛻䛶䚸䝗䝟䝭䞁㔞䛾ῶᑡ䜢䛥䜙䛻ᢚไ䛩䜛䚹䛣䜜䜙䛾 䛴䛾స⏝䛻䜘䜚䝗䝟䝭䞁㔞䛾పୗ䜢㜼Ṇ䛧䚸ቑຍ䛧䛯䝗䝟䝭䞁䛜ཷᐜయ䛾่⃭䜢ᣢ⥆ⓗ䛻㧗䜑 䜛䚹䛭䛾⤖ᯝ䜰䝉䝏䝹䝁䝸䞁䛾㐟㞳䛜ᢚไ䛥䜜䚸䝗䝟䝭䞁䛸䜰䝉䝏䝹䝁䝸䞁䛾䝞䝷䞁䝇䛜ㄪᩚ䛥䜜䛶 䝟䞊䜻䞁䝋䞁䛾≧䜢ᨵၿ䛩䜛䚹 (2) ⸆ຠ䜢䛡䜛ヨ㦂ᡂ⦼ 1) 㻹㻭㻻㻙㻮 㑅ᢥⓗ㜼ᐖຠᯝ㻌 MAO-B 䜢㑅ᢥⓗ䛻㜼ᐖ䛧䚸䛭䛾㑅ᢥᛶ䛿 MAO-A 䛻ᑐ䛩䜛స⏝䛾⣙1,000 ಸ䠄IC50䠅䛷䛒䛳䛯䚹 䜎䛯䚸䛭䛾స⏝䛿⃰ᗘ౫Ꮡⓗ䛻ㄆ䜑䜙䜜䠄I䠖䝷䝑䝖⬻䝩䝰䝆䝛䞊䝖䚸in vitro䠅䚸ྍ㏫ⓗ䛺㜼ᐖᵝ ᘧ䛷䛒䜛䛯䜑䚸స⏝䛿ᣢ⥆ⓗ䛷䛒䛳䛯䠄䊡䚸䊢䠖䝷䝑䝖⬻ෆ䚸in vivo䠅㻟㻜㻘㻟㻝㻕䚹 㻔㻑㻕㻌 㻝㻜㻜 㻹㻌 㻤㻜 㻭㻌 㻻㻌 㜼㻌 㻢㻜 ᐖ㻌 ⋡㻌 㻠㻜 㻞㻜 㻜 㻔㻑㻕㻌 㻝㻜㻜 㻥㻜 㻹㻭㻻㻙㻮㻌 㻹㻭㻻㻙㻮 㻹 䜰㻌 㻤㻜 㻭㻌 䝭㻌 㻣㻜 㻻 䞁㻌 㻢㻜 㜼 㻡㻜 䛾㻌 㻹㻭㻻㻙㻭 ᐖ 㻠㻜 ⃰㻌 ⋡ 㻟㻜 ᗘ㻌 㻹㻭㻻㻙㻭 㻞㻜 㻝㻜 㻔㼔㼞㻕㻌 㻔㻙㻸㼛㼓㻌㼏㼛㼚㼏㻚㻹㻕 㻜㻌 㻌 㻌 㻝㻌 㻌 㻌 㻞㻌 㻌 㻌 㻌 㻟㻌 㻌 㻌 㻠㻌 㻌 㻝㻜㻌 㻥㻌 㻤㻌 㻣㻌 㻢㻌 㻡㻌 㻠㻌 㻟㻌 㻞 䝉䝺䜼䝸䞁ሷ㓟ሷ㻌 䝉䝺䜼䝸䞁ሷ㓟ሷ⃰ᗘ ᢞᚋ䛾㛫㻌 㻔㻝㼙㼓㻛㼗㼓㻘㻌㼕㻚㼢㻚㻕㻌 㻔㼚㼙㼛㼘㻛㼓㻕㻌 㻣㻚㻜 㻢㻚㻜 䝗䝟䝭䞁 㻡㻚㻜 㻠㻚㻜 㻟㻚㻜 㻞㻚㻜 䝉䝻䝖䝙䞁㻌 䝜䝹䜶䝢䝛䝣䝸䞁 㻝㻚㻜 㻔㼔㼞㻕㻌 㻜㻌 㻝㻌 㻞㻌 㻟㻌 㻠 䝉䝺䜼䝸䞁ሷ㓟ሷ㻌 ᢞᚋ䛾㛫㻌 㻔㻝㼙㼓㻛㼗㼓㻘㻌㼕㻚㼢㻚㻕㻌 2) 㯮㉁㻙⥺᮲య䝗䝟䝭䞁⚄⤒䛻ཬ䜌䛩స⏝ 㯮 ㉁ - ⥺ ᮲ య 䝗 䝟 䝭 䞁 ⚄ ⤒ 䛾 㑅 ᢥ ⓗ ◚ ቯ ≀ ㉁ 䛷 䛒 䜛 MPTP 䠄 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine䠅䜢䝬䜴䝇䛻ᢞ䛩䜛䛸䚸㯮㉁䇲⥺᮲య䝗䝟䝭䞁⚄⤒䛾⬺ⴠ䛸䛸䜒 䛻⥺᮲య䝗䝟䝭䞁㔞䛿పୗ䛩䜛䚹䜘䛳䛶䚸MPTP 䛷㯮㉁䇲⥺᮲య䝗䝟䝭䞁⚄⤒䛾㞀ᐖ䜢㉳䛣䛥 䛫䚸䛭䛾㞀ᐖᗘ䜢⥺᮲య୰䛾䝗䝟䝭䞁䛸䛭䛾௦ㅰ≀䠄DOPAC䚸HVA䠅䛾ྵ㔞䛷ホ౯䛧䛯䚹䛭 䛾⤖ᯝ䚸䝉䝺䜼䝸䞁ሷ㓟ሷ䜢 MPTP ฎ⨨๓䛻ᢞ䛩䜛䛸䚸MPTP 䛻䜘䜛⥺᮲య䝗䝟䝭䞁㔞䛾 పୗ䜢ᢚไ䛧䛯 㻟㻞㻕䚹 䜎䛯䚸䝃䝹䛷䜒ྠᵝ䛻᳨ウ䛧䛯⤖ᯝ䚸䝉䝺䜼䝸䞁ሷ㓟ሷ䛿 MPTP 䛻䜘䜛⥺᮲య䝗䝟䝭䞁㔞䛾ప ୗ䜢ᢚไ䛧䛯 㻟㻟㻕䚹 17 3) ⥺᮲య䝗䝟䝭䞁⃰ᗘ䛾ቑຍస⏝ 㞝ᛶ䝷䝑䝖䜢⏝䛔䛯䝬䜲䜽䝻䝎䜲䜰䝸䝅䝇䠄⬻ෆᚤᑠ㏱ᯒἲ䠅䛻䜘䜛᳨ウ䛻䛶䚸༢ᅇᢞ䠄10.0 mg/kg䠅䚸3 㐌㛫䛾ᢞ䠄0.25䚸1.0mg/kg/᪥䠅䛾䛔䛪䜜䛻䛚䛔䛶䜒䝗䝟䝭䞁㔞䛾ቑຍ䛜☜ ㄆ䛥䜜䛯 㻟㻠㻕䚹 㻔㻑㻕㻌 㻔㻑㻕㻌 㻌 㻝㻞㻜㻜 吠吨吶呉⃰ᗘ叏ኚ⋡ 䖃䠖⏕⌮㣗ሷᾮ㻌 䕧䠖䝉䝺䜼䝸䞁ሷ㓟ሷ㻌 㻝㻚㻜㻌㼙㼓㻛㼗㼓㻌 䕦䠖䝉䝺䜼䝸䞁ሷ㓟ሷ㻌 㻞㻚㻡㻌㼙㼓㻛㼗㼓㻌 䕿䠖䝉䝺䜼䝸䞁ሷ㓟ሷ㻌 㻝㻜㻌㼙㼓㻛㼗㼓㻌 㻝㻜㻜㻜 㻤㻜㻜 㻢㻜㻜 㻠㻜㻜 ⾲ 㻌 㻞㻜㻜 㻜 㻜㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻢㻜 㻌 㻌 㻌 㻌 㻌 㻌 㻝㻞㻜 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻝㻤㻜 㻌 㻌 㻌 㻌 㻌 㻞㻠㻜 㻌 㛫㻌 㻔ศ㻕㻌 ㏱ᯒᾮ୰䛾䝗䝟䝭䞁⃰ᗘ䛻ᑐ䛩䜛䝉䝺䜼䝸䞁ሷ㓟ሷ༢ᅇ⭡⭍ෆᢞ䛾ᙳ㡪(n=6) (䊺)䛿䝉䝺䜼䝸䞁ሷ㓟ሷ䛸⏕⌮㣗ሷᾮ䛾ᢞ䜢♧䛩 *䠖P<0.05, #䠖P<0.10 (Kruskal-Wallis 䛸 Williams-Wilcoxon 䛾ከ㔜ẚ㍑᳨ᐃ), mean㼼S.E. ⥺᮲య⣽⬊እ䝗䝟䝭䞁ᅇ㔞䛻ᑐ䛩䜛䝉䝺䜼䝸䞁ሷ㓟ሷ 3 㐌㛫ᢞᚋ䛾ᙳ㡪 䝗䝟䝭䞁ᅇ㔞 ᢞ㔞 n ᢞ⤒㊰ ⸆≀ 䠄pg/20 ศ䠅 䠄mg/kg䠅 103.45㼼18.85 p.o. 12 䇷 ⏕⌮㣗ሷᾮ 191.09㼼44.48* p.o. 9 0.25 䝉䝺䜼䝸䞁ሷ㓟ሷ 253.88㼼56.63* p.o. 11 1.0 䝉䝺䜼䝸䞁ሷ㓟ሷ 237.82㼼50.72* i.p. 9 0.25 䝉䝺䜼䝸䞁ሷ㓟ሷ *䠖P䠘0.05䠄Kruskal-Wallis 䛸 Williams-Wilcoxon 䛾ከ㔜ẚ㍑᳨ᐃ䠅, mean㼼S.E. 䝃䝹䠄common marmoset䠅䛻䝉䝺䜼䝸䞁ሷ㓟ሷ 0.1mg/kg 䜢⭡⭍ෆὀᑕ䛷 2 㐌㛫ᢞ ᚋ䚸䜹䝹䝡䝗䝟 2.5mg/kg ཬ䜃䝺䝪䝗䝟 10.0mg/kg 䜢ᢞ䛧䚸䝬䜲䜽䝻䝎䜲䜰䝸䝅䝇䜢⏝䛔䛶⥺ ᮲య䛾⣽⬊እ䝗䝟䝭䞁⃰ᗘ䜢 ᐃ䛧䛯䚹ᢞ䛻䜘䜚䚸䝗䝟䝭䞁⃰ᗘ䛿䝁䞁䝖䝻䞊䝹⩌䛸ẚ㍑ 䛧䛶᭷ព䛻ቑຍ䛧䚸䛛䛴⬻ෆ᳨ฟ㛫䜒㢧ⴭ䛻ᘏ㛗䛧䛯 㻟㻡㻕䚹 㻔㼜㼓㻛㼟㼍㼙㼜㼘㼑㻕㻌 㻞㻜㻜 䕿䠖䝉䝺䜼䝸䞁ሷ㓟ሷ㻌 㻔㼚㻩㻡㻕㻌 䖃䠖䝁䞁䝖䝻䞊䝹㻌 㻌 㻌 㻌 㻌 㻔㼚㻩㻠㻕㻌 㻼㻨㻜㻚㻜㻡㻔㻹㼍㼚㼚㻙㼃㼔㼕㼠㼚㼑㼥 ᳨ᐃ㻕㻌 * * 䠖䠖㻼㻨㻜㻚㻜㻡㻔㻹㼍㼚㼚㻙㼃㼔㼕㼠㼚㼑㼥 㻝㻤㻜 ㏱ᯒᚋ叏吠吨吶呉㔞 㻝㻢㻜 㼙㼑㼍㼚㼟㼼㻿㻚㻱㻚㻌 㼙㼑㼍㼚㼼㻿㻚㻱㻚㻌 㻝㻠㻜 㻝㻞㻜 㻝㻜㻜 㻤㻜 㻢㻜 㻠㻜 㻞㻜 㻜 㻙㻢㻜㻌 㻔ศ㻕㻌 㻜㻌 㻢㻜㻌 㻝㻞㻜 㻝㻤㻜 㻞㻠㻜 㻟㻜㻜 㻌㛫 㻟㻢㻜 㻠㻞㻜 㻠㻤㻜 㻡㻠㻜㻌 2 㐌㛫ᢞヨ㦂䛻䛚䛡䜛⥺᮲య䛾⣽⬊እ䝗䝟䝭䞁⃰ᗘ 18 㻢㻜㻜㻌 㻌 4䠅 䝗䝟䝭䞁ྲྀ䜚㎸䜏㜼ᐖຠᯝ 䝷䝑䝖䛻䝉䝺䜼䝸䞁ሷ㓟ሷ 0.25mg/kg 䜢 14 ᪥㛫⓶ୗᢞ䛧䛯⤖ᯝ䚸䝷䝑䝖⥺᮲య䜈䛾 3H-䝗 䝟䝭䞁䛾ྲྀ䜚㎸䜏䛜㜼ᐖ䛥䜜䛯䛣䛸䛛䜙䚸䝅䝘䝥䝇㛫㝽䛷䛾䝗䝟䝭䞁㔞䛾ቑຍస⏝䛜♧၀䛥䜜 䛯 36)䚹 䝷䝑䝖⥺᮲యᶆᮏ୰䛾 3H-䝗䝟䝭䞁䛾ྲྀ䜚㎸䜏 ྲྀ䜚㎸䜎䜜䛯 3H-䝗䝟䝭䞁 䠄pmol/mg-protein䠅 ฎ ⨨ 䠄14 ᪥㛫⓶ୗᢞ䠅 462㼼32 359㼼31* ⏕⌮㣗ሷᾮ 䝉䝺䜼䝸䞁ሷ㓟ሷ䠄0.25mg/kg䠅 *䠖P䠘0.05 䠄Student's t-test䠅, mean㼼S.E., n=16 5) ⥺᮲య䛾ゎẘᶵᵓ䛻ཬ䜌䛩స⏝ ⚄⤒ኚᛶ䛻㛵䛩䜛䛸⪃䛘䜙䜜䜛䝣䝸䞊䝷䝆䜹䝹ཬ䜃䛭䛾㛵㐃≀㉁䛾ゎẘᶵᵓ䛻㛵䛧䚸䝉䝺 䜼䝸䞁ሷ㓟ሷ䛾ᢞ䛿ⱝ㱋䝷䝑䝖䛾⥺᮲య䛷䛾䝇䞊䝟䞊䜸䜻䝃䜲䝗䝆䝇䝮䝍䞊䝊䠄SOD䠅άᛶ 䜢䚸⪁㱋䝷䝑䝖䛾⥺᮲య䛷䛾 SOD άᛶཬ䜃䜹䝍䝷䞊䝊άᛶ䜢ቑຍ䛥䛫䛯 37,38)䚹 6) ⾑ᑠᯈ MAO-B άᛶ 䝠䝖⾑ᑠᯈ୰䛾 MAO 䛾Ṥ䛹䛜 B ᆺ䛷䛒䜛䛣䛸䛛䜙䚸⾑ᑠᯈ MAO-B άᛶ䛷⬻ෆ䛾 MAO-B άᛶ䛜䝰䝙䝍䝸䞁䜾ฟ᮶䜛䛸⪃䛘䜙䜜䛶䛔䜛 39,40)䚹 ᗣᡂே䛻 2.5䡚15.0mg ὀ䠅䜢༢ᅇ⤒ཱྀᢞ䛧䛯ሙྜ䚸7.5mg ௨ୖ䛾⏝㔞䛷䜋䜌䛻⾑ ᑠᯈ MAO άᛶ䛿㜼ᐖ䛥䜜䛯䠄䜶䝣䝢䞊㘄 2.5䠅11,27)䚹 䜎䛯䚸ᮎᲈᚠ⎔ෆ⾑ᑠᯈ MAO-B άᛶ䜢㏣㊧䛩䜛⮫ᗋ⸆⌮ヨ㦂䛻䛚䛔䛶䚸䝉䝺䜼䝸䞁ሷ㓟 ሷᢞ䛻䜘䜚䚸ᗣᡂே䚸䝟䞊䜻䞁䝋䞁ᝈ⪅䛸䜒䛻䚸ᢞᮇ㛫୰ MAO-B άᛶ䛿䚸䜋 䜌 100䠂㜼ᐖ䛥䜜䜛䛣䛸䛜ㄆ䜑䜙䜜䛯䠄䜶䝣䝢䞊㘄 2.5䠅8,11,12,27)䚹 ὀ䠅䜶䝣䝢䞊㘄 2.5 䛾ᢎㄆ䛥䜜䛯᭱ᢞ㔞䛿 10mg/᪥䛷䛒䜛䚹 (%) 100 80 ṧ Ꮡ 60 ά ᛶ 40 20 0 ๓ (n=5) 4 (n=2) 6 (n=1) 8 (n=3) 10 (n=3) 12 (n=2) ⾑ᑠᯈ MAO-B 䛾ṧᏑάᛶ䠄䝟䞊䜻䞁䝋䞁ᝈ⪅䠅 19 䠄㐌䠅 (3) స⏝Ⓨ⌧㛫䞉ᣢ⥆㛫㻌 1) స⏝Ⓨ⌧㛫 ヱᙜ㈨ᩱ䛺䛧䚹 2) స⏝ᣢ⥆㛫㻌 ᗣᡂே䛻 2.5䡚15.0mg ὀ䠅䜢༢ᅇ⤒ཱྀᢞ䛧䛯ሙྜ䚸⾑ᑠᯈ MAO άᛶ䛾㛫ⓗ᥎⛣䛿 ௨ୗ䛾䛸䛚䜚䛷䛒䛳䛯䚹1 㛫┠䛷䛿 2.5mg ᢞ䛷 50%䛜㜼ᐖ䚸5.0mg ᢞ䛷 80%䛜㜼ᐖ䚸 7.5mg䚸10.0mg䚸12.5mg䚸15.0mg ᢞ䛷 90%௨ୖ䛜㜼ᐖ䛥䜜䛯䚹24 㛫┠䚸48 㛫┠ 䛻䛚䛔䛶䜒 1 㛫┠䛸ྠ⛬ᗘ䛾㜼ᐖస⏝䛜ᣢ⥆䛧䛯䚹8 ᪥┠䛻䛿 MAO άᛶ䛿 50%௨ୖ䛻 ᅇ䛧䚸2 㐌㛫䛷䛻ᅇ䛧䛯䚹䛭䛾ᅇ㏿ᗘ䛿⏝㔞䛻౫Ꮡ䛫䛪䚸䜋䜌୍ᐃ䛾㏿ᗘ䛷䛒 䛳䛯䠄䜶䝣䝢䞊㘄 2.5䠅㻞㻣㻕䚹 ὀ䠅䜶䝣䝢䞊㘄 2.5 䛾ᢎㄆ䛥䜜䛯᭱ᢞ㔞䛿 10mg/᪥䛷䛒䜛䚹 䠖㻞㻚㻡㼙㼓 ༢ᅇᢞ⩌㻔㼚㻩㻟㻕㻌 䠖㻡㻚㻜㼙㼓 ༢ᅇᢞ⩌㻔㼚㻩㻟㻕㻌 䠖㻣㻚㻡㼙㼓 ༢ᅇᢞ⩌㻔㼚㻩㻟㻕㻌 䠖㻝㻜㻚㻜㼙㼓 ༢ᅇᢞ⩌㻔㼚㻩㻟㻕㻌 䠖㻝㻞㻚㻡㼙㼓 ༢ᅇᢞ⩌㻔㼚㻩㻟㻕㻌 䠖㻝㻡㻚㻜㼙㼓 ༢ᅇᢞ⩌㻔㼚㻩㻟㻕㻌 㻔㻑㻕 㻝㻡㻜 ⾑㻌 ᑠ㻌 ᯈ㻌 㻝㻜㻜 㻹㻌 㻭㻌 㻻㻌 㻡㻜 ά㻌 ᛶ 㻜 㻼㼞㼑㻌㻝 㻞㻠㻌 㻠㻤㻔㼔㼞㻕㻌 㻤 㻝㻟 㻌㛫 ༢ᅇᢞヨ㦂䛻䛚䛡䜛⾑ᑠᯈ MAO άᛶ䛾᥎⛣ 20 㻝㻡㻔㼐㼍㼥㻕㻌 䊦䠊⸆≀ືែ䛻㛵䛩䜛㡯┠ 䠍䠊 ⾑୰⃰ᗘ䛾᥎⛣䞉 ᐃἲ (1) ⒪ୖ᭷ຠ䛺⾑୰⃰ᗘ ヱᙜ㈨ᩱ䛺䛧䚹 (2) ᭱㧗⾑୰⃰ᗘ฿㐩㛫 ᗣᡂே䛻 2.5䡚15.0mg ὀ䠅䜢༢ᅇ⤒ཱྀᢞ䛧䛯ሙྜ䚸ᮍኚయ䛾 Tmax 䛿 0.08䡚2.42 㛫䛷 䛒䛳䛯䠄䜶䝣䝢䞊㘄 2.5䠅䚹 ὀ䠅䜶䝣䝢䞊㘄 2.5 䛾ᢎㄆ䛥䜜䛯᭱ᢞ㔞䛿 10mg/᪥䛷䛒䜛䚹 (3) ⮫ᗋヨ㦂䛷☜ㄆ䛥䜜䛯⾑୰⃰ᗘ 1) ㏻ᖖ⏝㔞䠄2.5䡚10.0mg䠅䛷䛾༢ᅇ⤒ཱྀᢞヨ㦂䠄ᗣᡂே䠅䛻䛚䛡䜛ᮍኚయ䛾⾑୰⃰ᗘ ⸆≀ືែ䝟䝷䝯䞊䝍䜢ୗ⾲䛻䜎䛸䜑䛯䠄䜶䝣䝢䞊㘄 2.5䠅䚹 ᢞヨ㦂䛷䛿䚸༢ᅇᢞ䛾⤖ᯝ䛛䜙ồ䜑䛯䝅䝭䝳䝺䞊䝅䝵䞁䜹䞊䝤䛻ᐇ ್䛜ẚ㍑ⓗ䜘 䛟୍⮴䛧䛶䛔䛯 27)䚹䜎䛯ᑠඣ䛻ᑐ䛩䜛ヱᙜ㈨ᩱ䛿䛺䛔䚹 㡯┠ ᢞ㔞 2.5mg 5.0mg 7.5mg 10.0mg Tmax 䠄hr䠅 0.17㼼0.10 0.67㼼0.20 2.42㼼2.21 0.08㼼0.10 Cmax 䠄ng/mL䠅 1.71㼼1.11 5.71㼼3.21 2.03㼼0.34 10.88㼼13.3 AUC0-48 䠄ng䞉hr/mL䠅 0.64㼼0.41 4.34㼼1.30 2.17㼼1.16 4.80㼼5.88 t1/2 䠄hr䠅 0.48㼼0.60 0.22㼼0.12 0.30㼼0.16 0.30㼼0.00 mean㼼S.E., n=6 2) ᗣᡂே䛻䚸䜶䝣䝢䞊OD 㘄 2.5 䜢 10.0mg䠄Ỉ䛺䛧䠅䛸䜶䝣䝢䞊㘄 2.5 䜢 10.0mg䠄Ỉ䛒䜚䠅䚸 ཬ䜃䜶䝣䝢䞊OD 㘄 2.5 䜢 10.0mg䠄Ỉ䛒䜚䠅䛸䜶䝣䝢䞊㘄 2.5 䜢 10.0mg䠄Ỉ䛒䜚䠅䛾᮲௳䛷༢ ᅇ⤒ཱྀᢞ䛧䛯䜽䝻䝇䜸䞊䝞䞊ヨ㦂䛻䛚䛔䛶䚸௦ㅰ≀䛷䛒䜛 N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁䛾⾑₢ ୰⃰ᗘ ᐃ䛾ヨ㦂⤖ᯝ䛿ḟ䛾䛸䛚䜚䛷䛒䛳䛯䚹䜶䝣䝢䞊OD 㘄 2.5 䛿 N-䝕䝇䝯䝏䝹䝉䝺䜼䝸 䞁䛻䛚䛔䛶䚸䜶䝣䝢䞊㘄 2.5 䛸⏕≀Ꮫⓗ䛻ྠ➼䛷䛒䜛䛣䛸䛜☜ㄆ䛥䜜䛯 41)䚹 21 䐟 䜶䝣䝢䞊OD 㘄 2.5 䜢 10.0mg䠄Ỉ䛺䛧䠅䛸䜶䝣䝢䞊㘄 2.5 䜢 10.0mg䠄Ỉ䛒䜚䠅䛷᭹⏝䛧 䛯䛸䛝䛾 N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁䛾ᖹᆒ⾑₢୰⃰ᗘ䛾᥎⛣ (ng/mL) 25 ⾑ ₢ 䝉 ୰ 䝺 N 䜼 卢 䝸 䝕 䞁 䝇 ⃰ 䝯 ᗘ 䝏 䝹 䜶䝣䝢䞊㘄㻞㻚㻡 䠄Ỉ䛒䜚䠅㻌㻝㻜䟘 20 䜶䝣䝢䞊㻻㻰㘄㻞㻚㻡 㻔Ỉ䛺䛧㻕㻌㻝㻜䟘 15 10 5 0 0 5 10 15 20 (hr) 㛫 ⾑₢୰ N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁⃰ᗘ䛾᥎⛣ 䠄mean, n=20䠅 ⸆≀ືែ䝟䝷䝯䞊䝍 AUCt 䠄ng䡡hr/mL䠅 Cmax 䠄ng/mL䠅 Tmax 䠄hr䠅 t1/2 䠄hr䠅 63.41㼼20.98 22.26㼼4.81 1.00㼼0.23 5.37㼼1.47 䜶䝣䝢䞊OD 㘄 2.5䠄Ỉ䛺䛧䛷᭹⏝䠅 62.36㼼25.98 21.32㼼7.58 1.03㼼0.47 5.29㼼1.59 ᢞ〇 䜶䝣䝢䞊㘄 2.5䠄Ỉ䛷᭹⏝䠅 meansS.D. 䐠 䜶䝣䝢䞊OD 㘄 2.5 䜢 10.0mg䠄Ỉ䛒䜚䠅䛸䜶䝣䝢䞊㘄 2.5 䜢 10.0mg䠄Ỉ䛒䜚䠅䛷᭹⏝䛧䛯 䛸䛝䛾 N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁䛾ᖹᆒ⾑₢୰⃰ᗘ䛾᥎⛣ (ng/mL) 25 ⾑ ₢ 䝉 ୰ 䝺 N 䜼 卢 䝸 䝕 䞁 䝇 ⃰ 䝯 ᗘ 䝏 䝹 䜶䝣䝢䞊㘄㻞㻚㻡 䠄Ỉ䛒䜚䠅㻌㻝㻜䟘 20 䜶䝣䝢䞊㻻㻰㘄㻞㻚㻡 㻔Ỉ䛒䜚㻕㻌㻝㻜䟘 15 10 5 0 0 5 10 15 20 (hr) 㛫 ⾑₢୰ N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁⃰ᗘ䛾᥎⛣ 䠄mean, n=20䠅 ⸆≀ືែ䝟䝷䝯䞊䝍 䜶䝣䝢䞊㘄 2.5䠄Ỉ䛷᭹⏝䠅 AUCt 䠄ng䡡hr/mL䠅 71.04㼼30.22 Cmax Tmax t1/2 䠄ng/mL䠅 䠄hr䠅 䠄hr䠅 22.27㼼7.31 1.03㼼0.34 5.12㼼1.86 䜶䝣䝢䞊OD 㘄 2.5䠄Ỉ䛷᭹⏝䠅 69.19㼼24.12 19.90㼼6.20 1.10㼼0.45 4.77㼼1.88 ᢞ〇 meansS.D. 22 3) 㧗㱋⪅ཬ䜃⫢䞉⭈ᶵ⬟㞀ᐖᝈ⪅䛾⸆≀ືែ 42) ᮏ䛷⒪䜢ཷ䛡䛶䛔䜛ᝈ⪅䛷⥔ᣢ㔞䛜 2.5mg/᪥䜎䛯䛿 5.0mg/᪥䠄ᮅ䞉㣗ᚋᢞ䠅䛾ᝈ ⪅䜢䚸Ϩ⩌䠄13 䠅䠖㠀㧗㱋䠄65 ṓᮍ‶䠅䛷⫢ཬ䜃⭈ᶵ⬟ṇᖖ⪅䚸ϩ⩌䠄15 䠅䠖㧗㱋䠄65 ṓ ௨ୖ䠅䛷⫢ཬ䜃⭈ᶵ⬟ṇᖖ⪅䚸Ϫ⩌䠄10 䠅䠖⭈ᶵ⬟ṇᖖ䛛䛴⫢ᶵ⬟␗ᖖᝈ⪅䠄ᖺ㱋ၥ䠅䚸 ϫ⩌䠄7 䠅䠖⫢ᶵ⬟ṇᖖ䛛䛴⭈ᶵ⬟␗ᖖᝈ⪅䠄ᖺ㱋ၥ䠅䛾 4 ⩌䛻ศ䛡䛯䚹ᮅ㣗ᚋ 2.5mg ᭹⏝ᚋ䚸䝉䝺䜼䝸䞁ཬ䜃௦ㅰ≀䛾⾑୰⃰ᗘ䜢 ᐃ䛧䚸ྛ⸆≀ືែ䝟䝷䝯䞊䝍䛻䛴䛔䛶Ϩ⩌䜢 ᑐ㇟䛻ϩ䡚ϫ⩌䜢ẚ㍑䛧䛯䚹䛭䛾⤖ᯝ䚸䛔䛪䜜䛾⩌䜒⾑୰䝉䝺䜼䝸䞁ᮍኚయ⃰ᗘ䛾᭷ព 䛺ୖ᪼䛿䜏䜙䜜䛪䚸䊡⩌䛷䛿䝟䝷䝯䞊䝍䛻᭷ពᕪ䜢ㄆ䜑䛺䛛䛳䛯䚹䊢⩌䛷䛿௦ㅰ≀䛷䛒䜛 "-䝯䝍䞁䝣䜵䝍䝭䞁䛾 Tmax 䛜㐜ᘏ䛧䚸ϫ⩌䛷䛿 N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁ཬ䜃"-䝯䝍䞁䝣䜵䝍䝭䞁 䛾 Tmax 䛜㐜ᘏ䛩䜛ഴྥ䛜ㄆ䜑䜙䜜䚸N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁䛾 AUC 䛾ቑຍ䚸䜽䝸䜰䝷䞁䝇 䠄CL䠅䛾పୗ䛜ㄆ䜑䜙䜜䛯䚹 ௨ୖ䚸ຍ㱋䛻䜘䜛ᮏ䛾⾑୰ືែ䜈䛾ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹䜎䛯䚸㍍ᗘ䛾⫢䞉⭈ᶵ⬟㞀 ᐖ䛜ᮏ䛾௦ㅰ䞉ἥ㏿ᗘ䛻䛘䜛ྍ⬟ᛶ䛜♧၀䛥䜜䛯䛜䚸⾑୰䝉䝺䜼䝸䞁䠋௦ㅰ≀⃰ᗘ 䛾ୖ᪼䛿ㄆ䜑䜙䜜䛪䚸⾑୰⃰ᗘ䛻䛘䜛ᙳ㡪䛿䜟䛪䛛䛷䛒䜛䛸⪃䛘䜙䜜䛯䚹 (4) ୰ẘᇦ ヱᙜ㈨ᩱ䛺䛧䚹 (5) 㣗䞉ే⏝⸆䛾ᙳ㡪 1) 㣗䛾ᙳ㡪 ➨䊠┦ヨ㦂 27䠅䛻䛚䛔䛶䚸ᗣᡂே䠄n=3䠅䛻 5.0mg 䜒䛧䛟䛿 10.0mg 䜢㣗๓ཪ䛿㣗ᚋ䛻⤒ཱྀ ᢞ䛧䛯䛸䛣䜝䚸䝉䝺䜼䝸䞁ᮍኚయ䚸௦ㅰ≀䛸䜒䛻㣗๓ᢞ䚸㣗ᚋᢞ䛾⾑୰⃰ᗘ䛿ྠ⛬ ᗘ䛷䛒䜛䛣䛸䛜ᚋゎᯒ䛻䜘䜚♧䛥䜜䛶䛔䜛䠄䜶䝣䝢䞊㘄 2.5䠅䚹୍᪉䚸ᗣᡂே䠄እᅜே䚸 n=11䠅䛻䛚䛔䛶䚸䝉䝺䜼䝸䞁ሷ㓟ሷ 5mg 䜢 1 ᪥ 2 ᅇ䠄ᮅ䛸䠅䚸✵⭡ཪ䛿㣗ᚋ䛻ᢞ䛩䜛䛸䚸 ✵⭡ᢞ䛻ẚ䜉䛶㣗ᚋᢞ䛷䛿䚸䝉䝺䜼䝸䞁䛾 Cmax ཬ䜃 AUCt 䛜᭷ព䛻ቑຍ䛧䛯䛸䛾ሗ ࿌䜒䛒䜛 43)䚹 2) ే⏝⸆䛾ᙳ㡪 䛂䊧䠊Ᏻᛶ䠄⏝ୖ䛾ὀព➼䠅䛻㛵䛩䜛㡯┠ 䠓䠊┦స⏝䛃䛾㡯䜢ཧ↷䚹 (6) ẕ㞟ᅋ䠄䝫䝢䝳䝺䞊䝅䝵䞁䠅ゎᯒ䛻䜘䜚ุ᫂䛧䛯⸆≀యෆືែኚືせᅉ ヱᙜ㈨ᩱ䛺䛧䚹 䠎䠊 ⸆≀㏿ᗘㄽⓗ䝟䝷䝯䞊䝍 (1) ゎᯒ᪉ἲ ヱᙜ㈨ᩱ䛺䛧䚹 (2) ྾㏿ᗘᐃᩘ ヱᙜ㈨ᩱ䛺䛧䚹 23 (3) 䝞䜲䜸䜰䝧䜲䝷䝡䝸䝔䜱 䝞䜲䜸䜰䝧䜲䝷䝡䝸䝔䜱䠄እᅜே䠅䠖⣙ 10䠂䠄10mg ༢ᅇᢞ䠅44) (4) ᾘኻ㏿ᗘᐃᩘ ᾘኻ㏿ᗘᐃᩘ䠄እᅜே䠅䠖0.0118min-1 䛊10mg ༢ᅇᢞ䚸ᗣᡂே䠄n=5䠅䛋45) (5) 䜽䝸䜰䝷䞁䝇 ⾑₢䜽䝸䜰䝷䞁䝇䠄እᅜே䠅䠖59.4L/min 䛊10mg ༢ᅇᢞ䚸ᗣᡂே䠄n=5䠅䛋45) (6) ศᕸᐜ✚ ศᕸᐜ✚䠄እᅜே䠅䠖1,854L䠄V/F䠅 䛊10mg ༢ᅇᢞ䚸ᗣᡂே䠄n=5䠅䛋45) (7) ⾑₢⺮ⓑ⤖ྜ⋡ ⾑₢⺮ⓑ⤖ྜ⋡䠄እᅜே䠅䠖93.79䡚78.05䠂46) 䝠䝖⾑₢䛻 14C-䝉䝺䜼䝸䞁ሷ㓟ሷ䜢 in vitro 䛷ຍ䛘䚸ྛ⃰ᗘ䠄0.027䡚0.271䃛g/mL䠅䛷䛾⺮ⓑ⤖ ྜ⋡䜢㝈እℐ㐣ἲ䛷 ᐃ䛧䛯䚹 䠏䠊 ྾ 䠘ཧ⪃䠚 䝡䞊䜾䝹≟䛻䝉䝺䜼䝸䞁ሷ㓟ሷ䠄3䚸10䚸30mg/kg䠅䜢⤒ཱྀᢞ䛧䛯⤖ᯝ䚸Cmax ཬ䜃 AUC0-24 䛸ᢞ 㔞䛾㛫䛻Ⰻዲ䛺┦㛵㛵ಀ䛜ㄆ䜑䜙䜜䛯 47,48)䚹 ື≀✀ ᢞ㔞 䝟䝷䝯䞊䝍 Tmax䠄hr䠅 Cmax䠄ng/mL䠅 AUC䠄ng䡡hr/mL䠅 t1/2䠄hr䠅 䝡䞊䜾䝹≟䠄n=5䠅 䝷䝑䝖䠄n=5䠅 30mg/kg 1.5mg/kg 2.20㼼0.97 3.00㼼0.89 0.25㼼0.1 53.12㼼17.61 164.64㼼36.14 571.67㼼223.69 120.38㼼11.98 662.88㼼273.08 2,427.55㼼746.18 1.36㼼0.32 1.16㼼0.27 3mg/kg 10mg/kg 0.70㼼0.12 2.28㼼0.80 288㼼24.6 1,723㼼77 3.75㼼0.5 mean㼼S.E. 䠐䠊 ศᕸ (1) ⾑ᾮ䇲⬻㛵㛛㏻㐣ᛶ 㟼⬦ෆᢞᚋ㏿䜔䛛䛻⬻䛻⛣⾜䛧䛯䠄እᅜே䠅49)䚹 䠘ཧ⪃䠚 ⬻ෆศᕸ䠄䝬䜴䝇䚸䝷䝑䝖䠅䠖䝬䜴䝇䛷䛿䚸㟼ὀ 30 ⛊ᚋ䛻䛿ᛴ㏿䛻୰ᯡ⚄⤒⣔䛻⛣⾜䛧䚸䛭䛾⃰ᗘ䛿 ⾑ᾮ୰䛾 3.5 ಸ䛷䛒䛳䛯 50) 䚹䜎䛯䚸䝷䝑䝖䜈䛾⤒ཱྀᢞ䛷䛿ᶆⓗ⮚ჾ䛷䛒䜛⬻ෆ䛾ᨺᑕ⬟⃰ᗘ䛿 ᢞ 0.5 㛫䛷್᭱䜢♧䛧䚸䛭䛾ᚋῶᑡ䛧䛯䛜䚸⫢⮚䚸ᾘ⟶ཬ䜃⭈⮚௨እ䛾⮚ჾෆ⃰ᗘ䛸 䛝䛺ᕪ䛿䛺䛟䚸䝉䝺䜼䝸䞁ሷ㓟ሷ䛜⾑ᾮ䠉⬻㛵㛛䜢㏻㐣䛧䛶⬻ෆ䛻⛣⾜䛩䜛䛣䛸䛜♧䛥䜜䛯 51)䚹 24 (2) ⾑ᾮ䇲⫾┙㛵㛛㏻㐣ᛶ 䠘ཧ⪃䠚 ⫾ඣ䜈䛾⛣⾜ᛶ䠄䝷䝑䝖䠅䠖ዷፎ 12 ᪥┠ཬ䜃 18 ᪥┠䛾䝷䝑䝖䛻⤒ཱྀᢞ䛧䛯䛾ẕయ⤌⧊ཬ䜃⫾ ඣ୰䛾ᨺᑕ⬟⃰ᗘ䛿ᢞᚋ 0.5 㛫䛷᭱㧗䛸䛺䜚䚸⫾ඣ୰⃰ᗘ䛿ẕయ⾑₢୰⃰ᗘ䜘䜚ప䛛䛳䛯䚹 ᭦䛻䚸3 㛫ᚋ䛛䜙䛾⃰ᗘ䛿ẕయ䚸⫾ඣඹ䛻ῶᑡ䛧䚸24 㛫ᚋ䛷䛿᳨ฟ㝈⏺௨ୗ䛒䜛䛔䛿㠀ᖖ 䛻ప್䛷䛒䛳䛯䚹䝉䝺䜼䝸䞁ሷ㓟ሷ䛻⫾ඣ⛣⾜ᛶ䛜䛒䜛䛣䛸䛜☜ㄆ䛥䜜䛯䛜䚸⫾ඣ䜈䛾✚ᛶ䛿 ప䛔䛸⪃䛘䜙䜜䜛 52)䚹 (3) ஙỒ୰䜈䛾⛣⾜ᛶ 䠘ཧ⪃䠚 ศፔᚋ 10 ᪥┠䛾ᤵங䝷䝑䝖䛻⤒ཱྀᢞ䛧䚸ஙỒ୰ཬ䜃ẕయ⾑୰⃰ᗘ䜢 ᐃ䛧䛯䚹䛭䛾⤖ᯝ䚸ங Ồ୰⃰ᗘ䛿ᢞᚋ 0.5 㛫䛷᭱㧗䛸䛺䜚䚸䛭䛾್䛿ẕయ⾑୰⃰ᗘ䛾 2 ಸ䛷䛒䛳䛯䚹ᢞ 3 㛫 ┠௨㝆䛛䜙䛿⾑୰⃰ᗘ䛸䜋䜌ྠ䛨⃰ᗘ䛷᥎⛣䛧䚸24 㛫ᚋ䛻䛿᳨ฟ㝈⏺௨ୗ䛸䛺䛳䛯䛣䛸䛛䜙䚸 䝉䝺䜼䝸䞁ሷ㓟ሷ䛿ஙỒ୰䛻ṧ␃䛩䜛䛣䛸䛿䛺䛔䛸⪃䛘䜙䜜䜛 53)䚹 (4) 㧊ᾮ䜈䛾⛣⾜ᛶ ヱᙜ㈨ᩱ䛺䛧䚹 (5) 䛭䛾䛾⤌⧊䜈䛾⛣⾜ᛶ 䠘ཧ⪃䠚 䝷䝑䝖䜈䛾⤒ཱྀᢞᚋ䛾㌟䜸䞊䝖䝷䝆䜸䜾䝷䝣䜱䞊䛷䛿䚸⮚ჾෆ䛾ᒁᅾ䛿⫶⭠⟶䚸⫢⮚䛷㠀ᖖ 䛻ከ䛟䚸ḟ䛔䛷⭈⮚䚸⭈䛷ከ䛟䚸⾑ᾮ䚸⫵䚸ၚᾮ⭢䚸➽⤌⧊ཬ䜃⓶䛿᭱䜒ᑡ䛺䛛䛳䛯䠄15 ศ䚸 30 ศ䠅䚹⬻䛷䛿䚸15 ศ䜘䜚 30 ศ䛾᪉䛜ከ䛛䛳䛯 48)䚹 25 䠑䠊 ௦ㅰ (1) ௦ㅰ㒊ཬ䜃௦ㅰ⤒㊰ 䝉䝺䜼䝸䞁ሷ㓟ሷ䛿⬻䛾 MAO-B 䛸ྍ㏫ⓗ䛻⤖ྜ䛩䜛䛣䛸䛻䜘䜚 MAO-B 䜢㜼ᐖ䛩䜛䛜䚸ᮍ ᛂ䛾䝉䝺䜼䝸䞁ሷ㓟ሷ䛿"-N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁ཬ䜃"-䝯䝍䞁䝣䜵䝍䝭䞁䛻௦ㅰ䛥䜜䜛 46)䚹䛭䜜䜙 䛾௦ㅰ≀䛾୍㒊䛿"-䜰䞁䝣䜵䝍䝭䞁䛻௦ㅰ䛥䜜䚸⦆ᚎ䛻ἥ䛥䜜䜛䛸᥎ᐃ䛥䜜䜛 54)䚹 䝉䝺䜼䝸䞁ሷ㓟ሷ "-N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁 "-䝯䝍䞁䝣䜵䝍䝭䞁 "-䜰䞁䝣䜵䝍䝭䞁 䝉䝺䜼䝸䞁ሷ㓟ሷ䛾᥎ᐃ௦ㅰ⤒㊰ (2) ௦ㅰ䛻㛵䛩䜛㓝⣲䛾ศᏊ✀ ᮏ䛿⫢⮚䛾䝏䝖䜽䝻䞊䝮 P-450 2D6 ཬ䜃 3A4 䛻䜘䛳䛶௦ㅰ䛥䜜䜛䚹 (3) ึᅇ㏻㐣ຠᯝ䛾᭷↓ཬ䜃䛭䛾ྜ ヱᙜ㈨ᩱ䛺䛧䚹 (4) ௦ㅰ≀䛾άᛶ䛾᭷↓ཬ䜃ẚ⋡ 䝉䝺䜼䝸䞁ሷ㓟ሷ䛾స⏝䛿 MAO-B 㜼ᐖస⏝䛷䛒䜛䛯䜑䚸⾑ᑠᯈ MAO άᛶ䠄90䠂௨ୖ䛜 B ᆺ䠅䛻ᑐ䛩䜛௦ㅰ≀䛾㜼ᐖຠᯝ䜢ẚ㍑䛧䛯䚹N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁䛿䚸10-6 M ௨ୗ䛷䛿㜼ᐖస ⏝䜢ㄆ䜑䛺䛔䛜䚸10-4 M 䛾㧗⃰ᗘ䛷䛿䝉䝺䜼䝸䞁ሷ㓟ሷ䛸ྠ⛬ᗘ䜎䛷㜼ᐖ䛧䛯䚹"-䝯䝍䞁䝣䜵䝍䝭䞁 䛷䛿 10-4 M 䜎䛷䝠䝖䛾⾑ᑠᯈ୰䛾 MAO άᛶ䜢㜼ᐖ䛧䛺䛛䛳䛯䠄䜶䝣䝢䞊㘄 2.5䠅55)䚹 26 (5) άᛶ௦ㅰ≀䛾㏿ᗘㄽⓗ䝟䝷䝯䞊䝍 ㏻ᖖ⏝㔞䠄2.5䡚10.0mg䠅䛷䛾༢ᅇ⤒ཱྀᢞヨ㦂䠄ᗣᡂே䠅䛻䛚䛡䜛 N-䝕䝇䝯䝏䝹䝉䝺䜼䝸䞁 䛾⾑୰⃰ᗘ⸆≀ືែ䝟䝷䝯䞊䝍䜢ୗ⾲䛻䜎䛸䜑䛯䠄䜶䝣䝢䞊㘄 2.5䠅27)䚹 㡯┠ ᢞ㔞 2.5mg 5.0mg 7.5mg 10.0mg Tmax 䠄hr䠅 Cmax 䠄ng/mL䠅 AUC0-48 䠄ng䡡hr/mL䠅 t1/2 䠄hr䠅 1.50㼼0.71 1.00㼼0.00 1.33㼼0.41 1.33㼼0.41 3.03㼼2.06 11.78㼼1.93 12.33㼼5.17 32.13㼼2.66 9.24㼼7.14 26.69㼼6.85 45.77㼼17.42 112.88㼼31.73 1.35㼼0.21 1.27㼼0.16 1.67㼼0.29 1.67㼼0.76 mean㼼S.E., n=6 䠒䠊 ἥ (1) ἥ㒊ཬ䜃⤒㊰ 䛸䛧䛶ᒀ୰䚹 (2) ἥ⋡ ᗣᡂே䛻 10.0mg/᪥䜢⤒ཱྀᢞ䛧䛯䛸䛝䚸ᒀ୰䜈ἥ䛥䜜䚸ᮍኚయཬ䜃௦ㅰ≀䛾 48 㛫ᒀ୰⣼✚ἥ⋡䜢 ᐃ䛩䜛䛸 34.5䠂䛷䛒䛳䛯䠄䜶䝣䝢䞊㘄 2.5䠅27)䚹 (3) ἥ㏿ᗘ ヱᙜ㈨ᩱ䛺䛧䚹 䠓䠊 䝖䝷䞁䝇䝫䞊䝍䞊䛻㛵䛩䜛ሗ ヱᙜ㈨ᩱ䛺䛧䚹 䠔䠊 ㏱ᯒ➼䛻䜘䜛㝖ཤ⋡ (1) ⭡⭷㏱ᯒ ヱᙜ㈨ᩱ䛺䛧䚹 (2) ⾑ᾮ㏱ᯒ ヱᙜ㈨ᩱ䛺䛧䚹 (3) ┤᥋⾑ᾮ℺ὶ ヱᙜ㈨ᩱ䛺䛧䚹 27 䊧䠊Ᏻᛶ䠄⏝ୖ䛾ὀព➼䠅䛻㛵䛩䜛㡯┠ 1䠊 ㆙࿌ෆᐜ䛸䛭䛾⌮⏤ ㆙࿌ (1) ᮏ䛸୕⎔⣔ᢠ䛖䛴䠄䜰䝭䝖䝸䝥䝏䝸䞁ሷ㓟ሷ➼䠅䛸䛾ే⏝䛿䛧䛺䛔䛣䛸䚹䜎䛯䚸ᮏ䛾ᢞ䜢୰ Ṇ䛧䛶䛛䜙୕⎔⣔ᢠ䛖䛴䛾ᢞ䜢㛤ጞ䛩䜛䛻䛿ᑡ䛺䛟䛸䜒 14 ᪥㛫䛾㛫㝸䜢⨨䛟䛣䛸䚹䠄䡞┦స ⏝䡟䛾㡯ཧ↷䠅 (2) ᮏ䛿⏝㔞䛾ቑຍ䛸䛸䜒䛻 MAO-B 䛾㑅ᢥⓗ㜼ᐖຠᯝ䛜పୗ䛧䚸㠀㑅ᢥⓗ MAO 㜼ᐖ䛻䜘䜛༴ 㝤ᛶ䛜䛒䜚䚸䜎䛯᭦䛺䜛ຠᯝ䛜ㄆ䜑䜙䜜䛺䛔䛯䜑䚸1 ᪥ 10mg 䜢㉸䛘䜛⏝㔞䜢ᢞ䛧䛺䛔䛣䛸䚹 䠄䡞㐣㔞ᢞ䡟䛾㡯ཧ↷䠅 (1) ୕⎔⣔ᢠ䛖䛴䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾ే⏝䛷㧗⾑ᅽ䚸ኻ⚄䚸⦰䚸Ⓨờ䚸䛶䜣䛛䜣䚸ືస䞉 ⢭⚄㞀ᐖ䛾ኚཬ䜃➽ᙉ๛䛸䛔䛳䛯స⏝䛜䛒䜙䜟䜜䚸䛥䜙䛻 2 䛾Ṛஸ䜢ㄆ䜑䛯䛣䛸䛜 WHO Drug Information 䛻ሗ࿌䛥䜜䛶䛔䜛䛯䜑 56)䚹 (2) ᮏ㑥䛷䛾䜶䝣䝢䞊㘄 2.5 䛾➨䊡┦ヨ㦂䛷 10mg/᪥䜎䛷䛧䛛⏝㔞౫Ꮡⓗ䛺ᨵၿ䛜ᚓ䜙䜜䛶䛚䜙䛪䚸 እᅜ䛷䛾⮫ᗋẚ㍑ヨ㦂䛷䜒 10mg/᪥䜢㉸䛘䜛⏝㔞䛷 10mg/᪥䛾ຠᯝ䜘䜚䛥䜙䛺䜛ຠᯝ䛜ㄆ䜑䜙 䜜䛶䛔䛺䛔䛯䜑䚹䜎䛯䚸⡿ᅜ⏝ୖ䛾ὀព䛾㆙࿌ཬ䜃㐣㔞ᢞ䛾ḍ䛻ྠᵝ䛾グ㍕䛜䛒䜚䚸ᮏ 䛾⏝䛻㝿䛧䛶㔜せ䛷䛒䜛䛸⪃䛘䜙䜜䛯䛯䜑䚹 䠎䠊 ⚗ᚷෆᐜ䛸䛭䛾⌮⏤ ⚗ᚷ䠄ḟ䛾ᝈ⪅䛻䛿ᢞ䛧䛺䛔䛣䛸䠅 (1) ᮏ䛾ᡂศ䛻ᑐ䛧㐣ᩄ䛾᪤ Ṕ䛾䛒䜛ᝈ⪅ (2) 䝨䝏䝆䞁ሷ㓟ሷ䚸䝖䝷䝬䝗䞊䝹ሷ㓟ሷཪ䛿䝍䝨䞁䝍䝗䞊䝹ሷ㓟ሷ䜢ᢞ୰䛾ᝈ⪅䠷㧗ᗘ䛾⯆ዧ䚸 ⢭⚄㘒➼䛾Ⓨ⌧䛜ሗ࿌䛥䜜䛶䛔䜛䚹䠹 (3) 㠀㑅ᢥⓗ䝰䝜䜰䝭䞁㓟㓝⣲㜼ᐖ䠄䝃䝣䝷䝆䞁ሷ㓟ሷ䠅䜢ᢞ୰䛾ᝈ⪅䠷㧗ᗘ䛾㉳❧ᛶప⾑ᅽ 䛾Ⓨ⌧䛜ሗ࿌䛥䜜䛶䛔䜛䚹䠹 (4) ⤫ྜኻㄪཪ䛿䛭䛾᪤ Ṕ䛾䛒䜛ᝈ⪅䠷⢭⚄≧䛾ᝏ䛜ሗ࿌䛥䜜䛶䛔䜛䚹䠹 (5) ぬ䛫䛔䚸䝁䜹䜲䞁➼䛾୰ᯡ⯆ዧ⸆䛾౫Ꮡཪ䛿䛭䛾᪤ Ṕ䛾䛒䜛ᝈ⪅ (6) ୕⎔⣔ᢠ䛖䛴䠄䜰䝭䝖䝸䝥䝏䝸䞁ሷ㓟ሷ➼䠅䜢ᢞ୰䛒䜛䛔䛿୰Ṇᚋ 14 ᪥㛫䛾ᝈ⪅䠄䡞┦స⏝䡟 䛾㡯ཧ↷䠅 (7) 㑅ᢥⓗ䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼ᐖ䠄䝣䝹䝪䜻䝃䝭䞁䝬䝺䜲䞁㓟ሷ➼䠅䚸䝉䝻䝖䝙䞁䞉䝜䝹䜰䝗䝺䝘䝸 䞁ྲྀ䜚㎸䜏㜼ᐖ䠄䝭䝹䝘䝅䝥䝷䞁ሷ㓟ሷ➼䠅䚸㑅ᢥⓗ䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏㜼ᐖ䠄䜰䝖 䝰䜻䝉䝏䞁ሷ㓟ሷ䠅ཪ䛿䝜䝹䜰䝗䝺䝘䝸䞁䞉䝉䝻䝖䝙䞁సືᛶᢠ䛖䛴䠄䝭䝹䝍䝄䝢䞁䠅䜢ᢞ୰䛾ᝈ ⪅䠄䛂┦స⏝䛃䛾㡯ཧ↷䠅 (1) 䜶䝣䝢䞊㘄 2.5 䛾స⏝䛷Ⓨ⑈䛜ぢ䜙䜜䛶䛔䜛䛯䜑䚹 (2) ᶵᗎ䛿᫂䛷䛒䜛䛜䚸䝨䝏䝆䞁ሷ㓟ሷ䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾㔜⠜䛺┦స⏝䛸䛧䛶䚸㧗ᗘ䛾⯆ ዧ䚸⢭⚄㘒➼䛾Ⓨ⌧䛜ᾏእ䛷ሗ࿌䛥䜜䛶䛔䜛䛯䜑 57)䚹䜎䛯䚸䝖䝷䝬䝗䞊䝹ሷ㓟ሷཬ䜃䝍䝨䞁䝍䝗 䞊䝹ሷ㓟ሷ䛿䝨䝏䝆䞁ሷ㓟ሷ䛸ྠᵝ䛾స⏝䜢♧䛩䛸⪃䛘䜙䜜䜛䛣䛸䛛䜙ὀពႏ㉳䜢⾜䛖䛯䜑䚹 (3) 䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾㔜⠜䛺┦స⏝䛸䛧䛶䚸㧗ᗘ䛾㉳❧ᛶప⾑ᅽ䛾Ⓨ⌧䛜ᾏእ䛷ሗ࿌䛥䜜䛶 䛔䜛䛯䜑 58)䚹 (4) 䜶䝣䝢䞊㘄 2.5 䛾⮫ᗋヨ㦂䛷䚸⤫ྜኻㄪ䜢ྜే䛩䜛䠄1 䠅䛻ᢞ䛧䛯䛸䛣䜝䚸㧗ᗘ䛾⢭⚄ ≧䛾Ⓨ⌧䜢ㄆ䜑䛯䛯䜑䚹䜎䛯䚸௦ㅰ≀䛷䛒䜛 "-䝯䝍䞁䝣䜵䝍䝭䞁䛺䛹䛾㛵䛾ྍ⬟ᛶ䛜ྰᐃ䛷 䛝䛺䛔䛯䜑䚹 (5) ᮏ䛾௦ㅰ≀䛸䛧䛶䚸"-䝯䝍䞁䝣䜵䝍䝭䞁䜔 "-䜰䞁䝣䜵䝍䝭䞁䛜ㄆ䜑䜙䜜䜛䛣䛸䛛䜙䚸䛭䜜䜙䛾స⏝䛜 ቑᙉ䛧䛯ሙྜ䚸䝣䝷䝑䝅䝳䝞䝑䜽䜢ᘬ䛝㉳䛣䛩䛣䛸䛜ྰᐃ䛷䛝䛺䛔䛯䜑䚹 (6) ୕⎔⣔ᢠ䛖䛴䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾ే⏝䛷㧗⾑ᅽ䚸ኻ⚄䚸⦰䚸Ⓨờ䚸䛶䜣䛛䜣䚸ືస䞉 28 ⢭⚄㞀ᐖ䛾ኚཬ䜃➽ᙉ๛䛸䛔䛳䛯స⏝䛜䛒䜙䜟䜜䚸䛥䜙䛻 2 䛾Ṛஸ䜢ㄆ䜑䛯䛣䛸䛜 WHO Drug Information 䛻ሗ࿌䛥䜜䛶䛔䜛䛯䜑 56)䚹 (7) 㑅ᢥⓗ䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼ᐖ䠄SSRI䠅59䡚64)䠖 ᾏእ䛻䛚䛔䛶䝉䝹䝖䝷䝸䞁ሷ㓟ሷ䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾ే⏝䛻䜘䜚䝉䝻䝖䝙䞁ೃ⩌䛾Ⓨ⌧䛜 ሗ࿌䛥䜜䛶䛚䜚䚸䜎䛯ྠᵝ䛾䛾 SSRI 䛷䛒䜛 Fluoxetine 䛸䛾ే⏝䛻䜘䜚䝉䝻䝖䝙䞁ೃ⩌䛻䜋 䜌୍⮴䛩䜛≧䛾Ⓨ⌧䛜ሗ࿌䛥䜜䛶䛔䜛䛯䜑䚹 䝉䝻䝖䝙䞁䞉䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏㜼ᐖ䠄SNRI䠅䠖 ᾏእ䛻䛚䛔䛶䝭䝹䝘䝅䝥䝷䞁ሷ㓟ሷཪ䛿䝕䝳䝻䜻䝉䝏䞁ሷ㓟ሷ䛸ྠᵝ䛾䛾 SNRI 䛷䛒䜛䝧䞁 䝷䝣䜯䜻䝅䞁ሷ㓟ሷ䛸䝰䝜䜰䝭䞁㓟㓝⣲㜼ᐖ Phenelzine 䛸䛾ే⏝䛻䜘䜛䝉䝻䝖䝙䞁ೃ⩌ 䛾Ⓨ⌧䛾ሗ࿌䛜䛒䜛䛯䜑 65)䚹 㑅ᢥⓗ䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏㜼ᐖ䠖 SNRI 䛸ྠᵝ䛾స⏝䜢♧䛩䛸⪃䛘䜙䜜䜛䛣䛸䛛䜙ὀពႏ㉳䜢⾜䛖䛯䜑䚹 䝜䝹䜰䝗䝺䝘䝸䞁䞉䝉䝻䝖䝙䞁సືᛶᢠ䛖䛴䠖 SSRI ཪ䛿 SNRI 䛸ྠᵝ䛾స⏝䜢♧䛩䛸⪃䛘䜙䜜䜛䛣䛸䛛䜙ὀពႏ㉳䜢⾜䛖䛯䜑䚹 䠏䠊 ຠ⬟ཪ䛿ຠᯝ䛻㛵㐃䛩䜛⏝ୖ䛾ὀព䛸䛭䛾⌮⏤ ヱᙜ䛧䛺䛔䚹 䠐䠊 ⏝ἲཬ䜃⏝㔞䛻㛵㐃䛩䜛⏝ୖ䛾ὀព䛸䛭䛾⌮⏤ 䛂䊤.⒪䛻㛵䛩䜛㡯┠䛃䛾㡯䜢ཧ↷䚹 䠑䠊 ៅ㔜ᢞෆᐜ䛸䛭䛾⌮⏤ ៅ㔜ᢞ䠄ḟ䛾ᝈ⪅䛻䛿ៅ㔜䛻ᢞ䛩䜛䛣䛸䠅 (1) 㔜⠜䛺⫢㞀ᐖ䛾䛒䜛ᝈ⪅䠷ᮏ䛾௦ㅰ䛜ᢚไ䛥䜜䚸ẘᛶ䛜ᖜ䛻ቑᙉ䛥䜜䜛ྍ⬟ᛶ䛜䛒䜛䚹䠹 (2) 㔜⠜䛺⭈㞀ᐖ䛾䛒䜛ᝈ⪅䠷ᮏ䛾௦ㅰ≀䛜✚䛥䜜䚸䛭䛾௦ㅰ≀䛻䜘䜛୰ᯡస⏝䛜⏕䛨䜛ྍ⬟ ᛶ䛜䛒䜛䚹䠹 (3) 㧗⏝㔞䛾䝺䝪䝗䝟ᢞ䜢ཷ䛡䛶䛔䜛ᝈ⪅䠷స⏝Ⓨ⌧⋡䛜㧗䛔䚹䠹 (4) 㧗㱋⪅䠷㉳❧ᛶప⾑ᅽ䛜䛒䜙䜟䜜䜔䛩䛔䚹䠹䠄䡞㧗㱋⪅䜈䛾ᢞ䡟䛾㡯ཧ↷䠅 (5) ᚰ䞉⬻ᚠ⎔ჾ⣔㞀ᐖ䜢᭷䛩䜛ᝈ⪅䠷ⱥᅜ䛻䛚䛔䛶䚸䝺䝪䝗䝟༢⊂⩌䛸䝉䝺䜼䝸䞁ሷ㓟ሷᢞᚋ䛻 䝺䝪䝗䝟䜢ే⏝ᢞ䛧䛯⩌䜢ẚ㍑䛧䛯ヨ㦂 29) 䛻䛚䛔䛶䚸䝺䝪䝗䝟༢⊂⩌䛻ᑐ䛧䛶䝉䝺䜼䝸䞁ሷ㓟 ሷᢞᚋ䛻䝺䝪䝗䝟ే⏝ᢞ䛧䛯⩌䛻ᚰ䞉⬻ᚠ⎔ჾ⣔㞀ᐖ䛻䜘䜛Ṛஸ䛜ከ䛛䛳䛯䛸ሗ࿌䛥䜜䛶 䛔䜛䚹䠹䠄䡞㔜せ䛺ᇶᮏⓗὀព(3)䡟䛾㡯ཧ↷䠅 (6) ⊃ᚰ䛾䛒䜛ᝈ⪅䠷ᮏ䛻䜘䜚ቑᝏ䛩䜛ྍ⬟ᛶ䛜䛒䜛䚹䠹 (1) ᮏ䛿⫢⮚䛾䝏䝖䜽䝻䞊䝮 P-450 䛷௦ㅰ䛥䜜䜛䛯䜑䚸⫢㞀ᐖᝈ⪅䛷䛿ᮏ䛾௦ㅰ䛜ᢚไ䛥䜜䚸 ẘᛶ䛜ᖜ䛻ቑᙉ䛥䜜䜛ྍ⬟ᛶ䛜䛒䜛䚹䜎䛯䚸⮫ᗋヨ㦂䛻䛶స⏝䛸䛧䛶⫢ᶵ⬟␗ᖖ䛜ㄆ䜑䜙 䜜䛶䛚䜚䚸䛥䜙䛻⫢㞀ᐖ䜢ቑᝏ䛥䛫䜛ྍ⬟ᛶ䛜⪃䛘䜙䜜䜛䛯䜑䚹 (2) ᮏཬ䜃ᮏ䛾௦ㅰ≀䛿䛸䛧䛶⭈⮚䛛䜙ฟ䛥䜜䚸≉䛻௦ㅰ≀䛷䛒䜛 "-䝯䝍䞁䝣䜵䝍䝭䞁䚸"-䜰 䞁䝣䜵䝍䝭䞁䛜✚䛥䜜䚸୰ᯡస⏝䛜⪃䛘䜙䜜䜛䛯䜑䚹 (3) 㧗⏝㔞䛾䝺䝪䝗䝟ᢞᝈ⪅䛾స⏝Ⓨ⌧⋡䛜㧗䛔䛯䜑䚹 (4) 䡞9. 㧗㱋⪅䜈䛾ᢞ䡟䛾㡯䜢ཧ↷䚹 (5) 䡞6. 㔜せ䛺ᇶᮏⓗὀព(3)䡟䛾㡯䜢ཧ↷䚹 (6) 㔜䛺స⏝䛾䛂⊃ᚰ䛃䛻䛚䛔䛶䚸䛂⊃ᚰ䛾Ⓨ⌧ཪ䛿ቑᝏ䛜ሗ࿌䛥䜜䛶䛔䜛䛃䛸グ㍕䛧䛶䛚䜚䚸 ⊃ᚰ䛾䛒䜛ᝈ⪅䛻ᑐ䛧䛶䛿ᢞ䛻ὀព䜢せ䛩䜛䛸⪃䛘䜙䜜䜛䛯䜑䚹 29 䠒䠊 㔜せ䛺ᇶᮏⓗὀព䛸䛭䛾⌮⏤ཬ䜃ฎ⨨᪉ἲ 㔜せ䛺ᇶᮏⓗὀព (1) ᮏ䛾ᢞ୰䛿䚸ᐃᮇⓗ䛻ຠᯝ䛜ᣢ⥆䛧䛶䛔䜛䛣䛸䜢☜ㄆ䛧䚸ຠᯝ䛜ᾘኻ䛧䛶䛔䜛ሙྜ䛿⏝䜢 ୰Ṇ䛧䚸ₔ↛䛸ᢞ䛧䛺䛔䛣䛸䚹 (2) 䜑䜎䛔䚸ὀពຊ䞉㞟୰ຊ䞉ᑕᶵ⬟➼䛾పୗ䛜㉳䛣䜛䛣䛸䛜䛒䜛䛾䛷䚸⮬ື㌴䛾㐠㌿䚸ᶵᲔ䛾᧯ స䚸㧗ᡤసᴗ➼༴㝤䜢క䛖సᴗ䛻ᚑ䛥䛫䛺䛔䜘䛖䛻ὀព䛩䜛䛣䛸䚹 (3) ⱥᅜ䛻䛚䛔䛶䚸᪩ᮇ䞉㍍䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛻䚸䝺䝪䝗䝟༢⊂⩌䛸䝉䝺䜼䝸䞁ሷ㓟ሷᢞ ᚋ䛻䝺䝪䝗䝟䜢ే⏝ᢞ䛧䛯⩌䜢ẚ㍑䛧䛯⚄⤒ಖㆤస⏝䛻㛵䛩䜛㛗ᮇ⮫ᗋヨ㦂䛜ᐇ䛥䜜 䛯䚹䛭䛾⤖ᯝ䚸䝺䝪䝗䝟༢⊂⩌䛾Ṛஸ⋡䛻ᑐ䛧䚸䝉䝺䜼䝸䞁ሷ㓟ሷᢞᚋ䛻䝺䝪䝗䝟䜢ే⏝ᢞ 䛧䛯⩌䛾Ṛஸ⋡䛜⣙ 1.6 ಸ䛸᭷ព䛻㧗䛛䛳䛯䛸䛾ሗ࿌ 29)䛜䛒䜛䚹䛭䛾ᚋ䛾㏣㊧ㄪᰝ 66)䛷䛿⣙ 1.3 ಸ㧗䛛䛳䛯䛜᭷ពᕪ䛿䛺䛛䛳䛯䛸䛾ሗ࿌䛜䛺䛥䜜䛶䛔䜛䚹䜎䛯䚸ⱥᅜ䛾་⸆ရᗇ䛜౫㢗䛧䛯 12,621 ே䛾୍⯡デ⒪䛾䝕䞊䝍䝧䞊䝇䜢⏝䛔䛯䝁䝩䞊䝖◊✲ 67)䛷䛿⣙ 1.1 ಸ㧗䛛䛳䛯䛜䚸᭷ពᕪ 䛿䛺䛛䛳䛯䛸䛾ሗ࿌䛜䛺䛥䜜䛶䛔䜛䚹䛥䜙䛻䚸ⱥᅜ௨እ䠄⡿ᅜ䚸䝜䝹䜴䜵䞊䚸䝇䜴䜵䞊䝕䞁䚸䝗䜲䝒䚸 䝣䜱䞁䝷䞁䝗䠅䛾 5 ヨ㦂䛾䝯䝍䜰䝘䝸䝅䝇䛾⤖ᯝ 68)䛷䛿⣙ 1.05 ಸ䛷᭷ពᕪ䛿䛺䛟䚸䜎䛯 2000 ᖺⱥ ᅜ䛾䝁䝩䞊䝖◊✲䛾ሗ࿌ 69)䛷䛿䚸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䝺䝪䝗䝟ే⏝ᝈ⪅䛾Ṛஸ⋡䛿ᖖே䛸ኚ䜟 䜙䛪䚸䝉䝺䜼䝸䞁ሷ㓟ሷ⒪䛻㛵㐃䛧䛯Ṛஸ⋡䛾ቑຍ䛿䛺䛔䛸ሗ࿌䛧䛶䛔䜛䚹 (1) せ䛺㛗ᮇᢞ䜢㑊䛡䚸䜘䜚Ᏻ䛻⏝䛩䜛䛯䜑䚹 (2) 䜶䝣䝢䞊㘄 2.5 䛾⢭⚄⚄⤒⣔䛾స⏝䛸䛧䛶䚸䡞䜑䜎䛔䞉䜅䜙䛴䛝䡟䚸䡞╀Ẽ䡟䛜ㄆ䜑䜙䜜䛶䛚䜚䚸༴ 㝤䜢క䛖సᴗ䛷䛾ᨾ㜵Ṇ䛾䛯䜑䚹 (3) ᘬ⏝ᩥ⊩ 29,66䡚69)䚹 30 䠓䠊 ┦స⏝ (1) ే⏝⚗ᚷ䛸䛭䛾⌮⏤ ే⏝⚗ᚷ䠄ే⏝䛧䛺䛔䛣䛸䠅 ⸆ྡ➼ ⮫ᗋ≧䞉ᥐ⨨᪉ἲ ᶵᗎ䞉༴㝤ᅉᏊ 䝨䝏䝆䞁ሷ㓟ሷ 䜸䝢䝇䝍䞁䒆➼ 䝖䝷䝬䝗䞊䝹ሷ㓟ሷ 䝖䝷䝬䞊䝹䒆➼ 䝍䝨䞁䝍䝗䞊䝹ሷ㓟ሷ 䝍䝨䞁䝍䒆 㧗ᗘ䛾⯆ዧ䚸⢭⚄㘒➼䛾Ⓨ ⌧䛜ሗ࿌䛥䜜䛶䛔䜛䚹䛺䛚䚸ᮏ 䛾ᢞ䜢୰Ṇ䛧䛶䛛䜙䝖䝷䝬 䝗䞊䝹ሷ㓟ሷཬ䜃䝍䝨䞁䝍䝗 䞊䝹ሷ㓟ሷ䛾ᢞ䜢㛤ጞ䛩䜛 䛻䛿ᑡ䛺䛟䛸䜒 14 ᪥㛫䛾㛫㝸 䜢⨨䛟䛣䛸䚹䜎䛯䝖䝷䝬䝗䞊䝹ሷ 㓟ሷ䛛䜙ᮏ䛻ษ䜚䛘䜛ሙ ྜ䛻䛿 2䡚3 ᪥㛫䛾㛫㝸䜢⨨䛟 䛣䛸䚹 ᶵᗎ䛿᫂䛷䛒䜛䚹 㠀㑅ᢥⓗ䝰䝜䜰䝭䞁㓟㓝⣲㜼ᐖ 䝃䝣䝷䝆䞁ሷ㓟ሷ 㧗ᗘ䛾㉳❧ᛶప⾑ᅽ䛾Ⓨ⌧ 䛜ሗ࿌䛥䜜䛶䛔䜛䚹 ヲ⣽䛿᫂䛷䛒䜛䛜䚸┦ ຍస⏝䛻䜘䜛䛸⪃䛘䜙䜜 䜛䚹 ୕⎔⣔ᢠ䛖䛴 䜰䝭䝖䝸䝥䝏䝸䞁ሷ㓟ሷ➼ 䝖䝸䝥䝍䝜䞊䝹䒆➼ 㧗⾑ᅽ䚸ኻ⚄䚸⦰䚸Ⓨ ờ䚸䛶䜣䛛䜣䚸ືస䞉⢭⚄㞀ᐖ 䛾ኚཬ䜃➽ᙉ๛䛸䛔䛳䛯 స⏝䛜䛒䜙䜟䜜䚸᭦䛻Ṛஸ 䜒ሗ࿌䛥䜜䛶䛔䜛䚹 ヲ⣽䛿᫂䛷䛒䜛䛜䚸┦ ຍ䞉┦స⏝䛻䜘䜛䛸⪃䛘 䜙䜜䜛䚹 㑅ᢥⓗ䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼ᐖ 䝣䝹䝪䜻䝃䝭䞁䝬䝺䜲䞁㓟ሷ 䝹䝪䝑䜽䝇䒆➼ 䝟䝻䜻䝉䝏䞁ሷ㓟ሷỈ≀ 䝟䜻䝅䝹䒆 䝉䝹䝖䝷䝸䞁ሷ㓟ሷ 䝆䜵䜲䝌䝻䝣䝖 TM 䜶䝇䝅䝍䝻䝥䝷䝮䝅䝳䜴㓟ሷ 䝺䜽䝃䝥䝻䒆 ୧⸆䛾స⏝䛜ቑᙉ䛥䜜䜛ྍ ⬟ᛶ䛜䛒䜛䛾䛷䚸ᮏ䛾ᢞ 䜢୰Ṇ䛧䛶䛛䜙㑅ᢥⓗ䝉䝻䝖䝙 䞁ྲྀ䜚㎸䜏㜼ᐖ䚸䝉䝻䝖䝙 䞁䞉䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏 㜼ᐖ䚸㑅ᢥⓗ䝜䝹䜰䝗䝺䝘䝸 䞁ྲྀ䜚㎸䜏㜼ᐖཬ䜃䝜䝹 䜰䝗䝺䝘䝸䞁䞉䝉䝻䝖䝙䞁సືᛶ ᢠ䛖䛴䛾ᢞ䜢㛤ጞ䛩䜛䛻 䛿ᑡ䛺䛟䛸䜒 14 ᪥㛫䛾㛫㝸䜢 ⨨䛟䛣䛸䚹䜎䛯ᮏ䛻ษ䜚䛘䜛 ሙྜ䛻䛿䝣䝹䝪䜻䝃䝭䞁䝬䝺䜲 䞁㓟ሷཬ䜃䝧䞁䝷䝣䜯䜻䝅䞁ሷ 㓟ሷ䛿 7 ᪥㛫䚸䝟䝻䜻䝉䝏䞁 ሷ㓟ሷỈ≀䚸䝉䝹䝖䝷䝸䞁ሷ 㓟ሷ䚸䜰䝖䝰䜻䝉䝏䞁ሷ㓟ሷ䚸 䝭䝹䝍䝄䝢䞁ཬ䜃䜶䝇䝅䝍䝻䝥 䝷䝮䝅䝳䜴㓟ሷ䛿 14 ᪥㛫䚸䝭䝹 䝘䝅䝥䝷䞁ሷ㓟ሷ䛿 2䡚3 ᪥ 㛫䚸䝕䝳䝻䜻䝉䝏䞁ሷ㓟ሷ䛿 5 ᪥㛫䛾㛫㝸䜢⨨䛟䛣䛸䚹 䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼ᐖ స⏝䛜䛒䜛䛯䜑⬻ෆ䝉䝻 䝖䝙䞁⃰ᗘ䛜㧗䜎䜛䛸⪃䛘 䜙䜜䛶䛔䜛䚹 䝉䝻䝖䝙䞁䡡䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚 ㎸䜏㜼ᐖ 䝭䝹䝘䝅䝥䝷䞁ሷ㓟ሷ 䝖䝺䝗䝭䞁䒆 䝕䝳䝻䜻䝉䝏䞁ሷ㓟ሷ 䝃䜲䞁䝞䝹䝍䒆 䝧䞁䝷䝣䜯䜻䝅䞁ሷ㓟ሷ 䜲䝣䜵䜽䝃䞊䒆 㑅ᢥⓗ䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏 㜼ᐖ 䜰䝖䝰䜻䝉䝏䞁ሷ㓟ሷ 䝇䝖䝷䝔䝷䒆 ⬻ෆ䝰䝜䜰䝭䞁⥲㔞䛾ቑ ຍ䛜⪃䛘䜙䜜䛶䛔䜛䚹 ⬻ෆ䝜䝹䜰䝗䝺䝘䝸䞁䚸䝉 䝻䝖䝙䞁䛾⚄⤒ఏ㐩䛜㧗 䜎䜛䛸⪃䛘䜙䜜䛶䛔䜛䚹 䝜䝹䜰䝗䝺䝘䝸䞁䞉䝉䝻䝖䝙䞁సືᛶ ᢠ䛖䛴 䝭䝹䝍䝄䝢䞁 䝺䝯䝻䞁䒆➼ 1) 䝨䝏䝆䞁ሷ㓟ሷ䚸䝖䝷䝬䝗䞊䝹ሷ㓟ሷ䚸䝍䝨䞁䝍䝗䞊䝹ሷ㓟ሷ ᶵᗎ䛿᫂䛷䛒䜛䛜䚸䝨䝏䝆䞁ሷ㓟ሷ䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾㔜⠜䛺┦స⏝䛸䛧䛶䚸㧗ᗘ䛾 ⯆ዧ䚸⢭⚄㘒➼䛾Ⓨ⌧䛜ᾏእ䛷ሗ࿌䛥䜜䛶䛔䜛 57)䚹 䝖䝷䝬䝗䞊䝹ሷ㓟ሷཬ䜃䝍䝨䞁䝍䝗䞊䝹ሷ㓟ሷ䛿䝨䝏䝆䞁ሷ㓟ሷ䛸ྠᵝ䛾స⏝䜢♧䛩䛸⪃䛘 31 2) 3) 4) 5) 6) 7) 䜙䜜䜛䛣䛸䛛䜙ὀពႏ㉳䜢⾜䛖䛯䜑䚹 㠀㑅ᢥⓗ䝰䝜䜰䝭䞁㓟㓝⣲㜼ᐖ 䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾㔜⠜䛺┦స⏝䛸䛧䛶䚸㧗ᗘ䛾㉳❧ᛶప⾑ᅽ䛾Ⓨ⌧䛜ᾏእ䛷ሗ࿌䛥䜜 䛶䛔䜛䛯䜑 58)䚹 ୕⎔⣔ᢠ䛖䛴 ୕⎔⣔ᢠ䛖䛴䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾ే⏝䛷㧗⾑ᅽ䚸ኻ⚄䚸⦰䚸Ⓨờ䚸䛶䜣䛛䜣䚸ື స䞉⢭⚄㞀ᐖ䛾ኚཬ䜃➽ᙉ๛䛸䛔䛳䛯స⏝䛜䛒䜙䜟䜜䚸䛥䜙䛻 2 䛾Ṛஸ䜢ㄆ䜑䛯䛣䛸 䛜 WHO Drug Information 䛻ሗ࿌䛥䜜䛶䛔䜛䛯䜑 56)䚹 㑅ᢥⓗ䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼ᐖ䠄SSRI䠅59䡚64) ᾏእ䛻䛚䛔䛶䝉䝹䝖䝷䝸䞁ሷ㓟ሷ䛸䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛾ే⏝䛻䜘䜚䝉䝻䝖䝙䞁ೃ⩌䛾Ⓨ⌧ 䛜ሗ࿌䛥䜜䛶䛚䜚䚸䜎䛯ྠᵝ䛾䛾 SSRI 䛷䛒䜛 Fluoxetine 䛸䛾ే⏝䛻䜘䜚䝉䝻䝖䝙䞁ೃ⩌ 䛻䜋䜌୍⮴䛩䜛≧䛾Ⓨ⌧䛜ሗ࿌䛥䜜䛶䛔䜛䛯䜑䚹 䝉䝻䝖䝙䞁䡡䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏㜼ᐖ䠄SNRI䠅 ᾏእ䛻䛚䛔䛶䝭䝹䝘䝅䝥䝷䞁ሷ㓟ሷཪ䛿䝕䝳䝻䜻䝉䝏䞁ሷ㓟ሷ䛸ྠᵝ䛾䛾 SNRI 䛷䛒䜛䝧 䞁䝷䝣䜯䜻䝅䞁ሷ㓟ሷ䛸䝰䝜䜰䝭䞁㓟㓝⣲㜼ᐖ Phenelzine 䛸䛾ే⏝䛻䜘䜛䝉䝻䝖䝙䞁ೃ ⩌䛾Ⓨ⌧䛾ሗ࿌䛜䛒䜛䛯䜑 65)䚹 㑅ᢥⓗ䝜䝹䜰䝗䝺䝘䝸䞁ྲྀ䜚㎸䜏㜼ᐖ SNRI 䛸ྠᵝ䛾స⏝䜢♧䛩䛸⪃䛘䜙䜜䜛䛣䛸䛛䜙ὀពႏ㉳䜢⾜䛖䛯䜑䚹 䝜䝹䜰䝗䝺䝘䝸䞁䞉䝉䝻䝖䝙䞁సືᛶᢠ䛖䛴 SSRI ཪ䛿 SNRI 䛸ྠᵝ䛾స⏝䜢♧䛩䛸⪃䛘䜙䜜䜛䛣䛸䛛䜙ὀពႏ㉳䜢⾜䛖䛯䜑䚹 (2) ే⏝ὀព䛸䛭䛾⌮⏤ ే⏝ὀព䠄ే⏝䛻ὀព䛩䜛䛣䛸䠅 ⸆ྡ➼ ⮫ᗋ≧䞉ᥐ⨨᪉ἲ ᶵᗎ䞉༴㝤ᅉᏊ ⫢⮚䛾䝏䝖䜽䝻䞊䝮 P-450 2D6 ཬ䜃 ᮏ䛾స⏝䚸ẘᛶ䛜ᖜ䛻ቑ 3A4 䛾㜼ᐖస⏝䜢᭷䛩䜛〇 ὀ 1) ᙉ䛥䜜䜛ྍ⬟ᛶ䛜䛒䜛䚹 䝅䝯䝏䝆䞁 䜻䝙䝆䞁◲㓟ሷ 䝥䝻䝟䝣䜵䝜䞁ሷ㓟ሷ 䝝䝻䝨䝸䝗䞊䝹 䜶䝸䝇䝻䝬䜲䝅䞁 䝆䝵䝃䝬䜲䝅䞁 䜽䝷䝸䝇䝻䝬䜲䝅䞁 䜲䝖䝷䝁䝘䝌䞊䝹 䝣䝹䝁䝘䝌䞊䝹 䝭䝁䝘䝌䞊䝹 䜽䝻䝖䝸䝬䝌䞊䝹 䜶䝏䝙䝹䜶䝇䝖䝷䝆䜸䞊䝹 䝧䝷䝟䝭䝹ሷ㓟ሷ 䝆䝹䝏䜰䝊䝮ሷ㓟ሷ➼ ᮏ䛿⫢⮚䛾䝏䝖䜽䝻䞊 䝮 P-450 2D6 ཬ䜃 3A4 䛻䜘䛳䛶௦ㅰ䛥䜜䜛䛣䛸䛜 ุ᫂䛧䛶䛚䜚䚸䛣䜜䜢㜼 ᐖ䛩䜛⸆䛸䛾ే⏝䛻䜘 䜚⾑୰⃰ᗘ䛾ୖ᪼䜢䜒䛯 䜙䛩䚹 䝺䝉䝹䝢䞁ㄏᑟయ 䝺䝉䝹䝢䞁➼ ᮏ䛾స⏝䛜ῶᙅ䛥䜜䜛ྍ⬟ ᛶ䛜䛒䜛䚹 ⬻ෆ䝗䝟䝭䞁䜢ῶᑡ䛥䛫 䜛䚹 䝣䜵䝜䝏䜰䝆䞁⣔⸆ 䝥䝻䜽䝻䝹䝨䝷䝆䞁 䜽䝻䝹䝥䝻䝬䝆䞁 䝨䝷䝆䞁➼ 䝤䝏䝻䝣䜵䝜䞁⣔⸆ 䝤䝻䝮䝨䝸䝗䞊䝹➼ 䝇䝹䝢䝸䝗 䝯䝖䜽䝻䝥䝷䝭䝗 ᮏ䛾స⏝䛜ῶᙅ䛥䜜䜛ྍ⬟ ᛶ䛜䛒䜛䚹 ⬻ෆ䝗䝟䝭䞁ཷᐜయ䜢㐽 ᩿䛩䜛䚹 32 ⸆ྡ➼ ⮫ᗋ≧䞉ᥐ⨨᪉ἲ ᶵᗎ䞉༴㝤ᅉᏊ 䝖䝷䝌䝗䞁ሷ㓟ሷ ┦స⏝䛿᫂䜙䛛䛻䛺䛳䛶䛔 䛺䛔䛜䚸䝖䝷䝌䝗䞁ሷ㓟ሷ䛾୰ Ṇ┤ᚋ䛒䜛䛔䛿ే⏝䛩䜛ሙྜ 䛻䛿䚸ᮏ䛾ᢞ㔞䜢ᚎ䚻䛻 ቑຍ䛩䜛䛺䛹䚸ៅ㔜䛻ᢞ䜢 㛤ጞ䛩䜛䛣䛸䚹 䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼 ᐖస⏝䛜䛒䜛䛯䜑⬻ෆ䝉 䝻䝖䝙䞁⃰ᗘ䛜㧗䜎䜛䛸⪃ 䛘䜙䜜䛶䛔䜛䚹 ឤ⚄⤒⯆ዧ 䜶䝣䜵䝗䝸䞁ሷ㓟ሷ 䝯䝏䝹䜶䝣䜵䝗䝸䞁ሷ㓟ሷ 䝥䝋䜲䝗䜶䝣䜵䝗䝸䞁ሷ㓟ሷྵ᭷་ ⸆ရ 䝣䜵䝙䝹䝥䝻䝟䝜䞊䝹䜰䝭䞁ሷ㓟 ሷྵ᭷་⸆ရ ⾑ᅽୖ᪼䚸㢖⬦➼䛾Ⓨ⌧䛜ሗ ࿌䛥䜜䛶䛔䜛䚹 ᮏ䛾 MAO-B 㑅ᢥᛶ 䛜పୗ䛧䛯ሙྜ䚸ឤ⚄ ⤒่⃭స⏝䛜ቑᙉ䛥䜜 䜛䛸⪃䛘䜙䜜䜛䚹 ὀ1䠅 䛣䜜䜙䛾⸆䛸ే⏝䛩䜛ሙྜ䛻䛿䝰䝜䜰䝭䞁ྵ᭷㔞䛾ከ䛔㣗≀䠄䝏䞊䝈䚸䝺䝞䞊䚸䛻䛧䜣䚸㓝ẕ䚸䛭䜙㇋䚸 䝞䝘䝘䚸䝡䞊䝹䚸䝽䜲䞁➼䠅䛸䛾ే⏝䛻䛿ὀព䛩䜛䛣䛸䚹䠷䝏䝖䜽䝻䞊䝮 P-450 2D6 ཬ䜃 3A4 䜢㜼ᐖ䛩䜛 ⸆䛸ే⏝䛩䜛ሙྜ䛻䛿ᮏ䛾⾑୰⃰ᗘ䛜ୖ᪼䛧䚸MAO-B 䛾㑅ᢥᛶ䛜ᾘኻ䛩䜛ྍ⬟ᛶ䛜䛒䜛䚹䠹 1) ⫢⮚䛾䝏䝖䜽䝻䞊䝮 P-450 2D6 ཬ䜃 3A4 䛾㜼ᐖస⏝䜢᭷䛩䜛〇 ᮏ䛿⫢⮚䛾䝏䝖䜽䝻䞊䝮 P-450 2D6 ཬ䜃 3A4 䛷௦ㅰ䛥䜜䜛䛯䜑 70,71䠅䚹 ὀ 1䠅 ᮏ䛿䝏䝖䜽䝻䞊䝮 P-450 2D6 ཬ䜃 3A4 䛻䜘䛳䛶௦ㅰ䛥䜜䜛䛣䛸䛜ุ᫂䛧䛶䛚䜚䚸䛣䜜 䜢㜼ᐖ䛩䜛⸆䛸䛾ే⏝䛻䜘䜚⾑୰⃰ᗘ䛾ୖ᪼䜢䜒䛯䜙䛧䛯ሙྜ䚸䝏䝷䝭䞁ྵ᭷䛾ከ䛔 㣗≀䛾ᦤྲྀ䛿␗ᖖ᪼ᅽ䜢ᣍ䛟䛚䛭䜜䛜䛒䜛䛯䜑䚹 2) 䝺䝉䝹䝢䞁ㄏᑟయ䚸䝣䜵䝜䝏䜰䝆䞁⣔⸆䚸䝤䝏䝻䝣䜵䝜䞁⣔⸆䚸䝇䝹䝢䝸䝗䚸䝯䝖䜽䝻䝥䝷䝭䝗 ᮏ䛾⸆⌮స⏝䛿⬻ෆ䝗䝟䝭䞁䛾ศゎᢚไ䛻䛒䜚䚸⬻ෆ䝗䝟䝭䞁㔞䜢ῶᑡ䛥䛫䜛⸆ཪ䛿⬻ ෆ䝗䝟䝭䞁ཷᐜయ䜢㐽᩿䛩䜛⸆䛸䛾ే⏝䛻䜘䜚䚸⤖ᯝⓗ䛻ᮏ䛾⮫ᗋຠᯝ䛜ῶᙅ䛥䜜䜛ྍ ⬟ᛶ䛜⪃䛘䜙䜜䜛䚹䜘䛳䛶䚸グ㍕ෆᐜ䛿䚸ᮏ䛾ྠຠᯝ䛷䛒䜛䝺䝪䝗䝟ྵ᭷〇䛻ྜ䜟䛫䚸 ⬻ෆ䝗䝟䝭䞁䜢ῶᑡ䛩䜛䜒䛾䛸ཷᐜయ䛻ᙳ㡪䛩䜛䜒䛾䛸䛻ศ䛡䛶グ㍕䛧䛯䚹 3) 䝖䝷䝌䝗䞁ሷ㓟ሷ 䝖䝷䝌䝗䞁ሷ㓟ሷ䛿䚸䝉䝻䝖䝙䞁ྲྀ䜚㎸䜏㜼ᐖస⏝䜢᭷䛩䜛䛣䛸䛛䜙䚸ᮏ䛸䛾ే⏝䛻䜘䜚⬻ ෆ䝉䝻䝖䝙䞁⃰ᗘ䛜㧗䛟䛺䜛䛸⪃䛘䜙䜜䜛䛯䜑䚹 4) ឤ⚄⤒⯆ዧ 72䠅 ᮏ䛸ឤ⚄⤒⯆ዧ䠄䜶䝣䜵䝗䝸䞁ሷ㓟ሷ䚸䝯䝏䝹䜶䝣䜵䝗䝸䞁ሷ㓟ሷ䚸䝥䝋䜲䝗䜶䝣䜵䝗䝸䞁 ሷ㓟ሷྵ᭷་⸆ရ䚸䝣䜵䝙䝹䝥䝻䝟䝜䞊䝹䜰䝭䞁ሷ㓟ሷྵ᭷་⸆ရ䠅䛾ే⏝䛻㝿䛧䛶䚸ᮏ 䛾㐣㔞ᢞ➼䛻䜘䜚 MAO-B 㜼ᐖ䛾㑅ᢥᛶ䛜పୗ䛧䛯ሙྜ䚸䛭䛾స⏝ᶵᗎ䛛䜙 MAO-A 䜒 㜼ᐖ䛥䜜䜛ྍ⬟ᛶ䛜䛒䜚䚸䜶䝣䜵䝗䝸䞁䛾่⃭䛻䜘䜚ᨺฟ䛥䜜䛯䝜䝹䜰䝗䝺䝘䝸䞁䛾௦ㅰ䜢㜼ᐖ 䛩䜛䛣䛸䛜⪃䛘䜙䜜䜛䚹䛭䛾⤖ᯝ䛸䛧䛶䚸䝜䝹䜰䝗䝺䝘䝸䞁䛾⾑୰⃰ᗘ䛾ቑຍ䛻䜘䛳䛶⾑ᅽୖ᪼ 䜔㢖⬦➼䛾ᚠ⎔ჾ⣔㞀ᐖ䛜Ⓨ⌧䛩䜛ྍ⬟ᛶ䛜䛻ྰᐃ䛷䛝䛺䛔䛯䜑䚹 33 䠔䠊 స⏝ (1) స⏝䛾ᴫせ 䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅ 488 ୰ 177 䠄36.3䠂䠅䛻స⏝䛜 ㄆ䜑䜙䜜䛯䚹䛺స⏝䛿ᝏᚰ䞉ྤ䠄7.8䠂䠅䚸䝆䝇䜻䝛䝆䜰䠄6.6䠂䠅䚸ᗁぬ䠄6.6䠂䠅䚸㣗ḧ 䠄6.1䠂䠅䚸䜑䜎䛔䞉䜅䜙䛴䛝䠄5.7䠂䠅䛷䛒䛳䛯䚹䜎䛯⮫ᗋ᳨ᰝ್䛾䛺␗ᖖኚື䛸䛧䛶䛿䚸䝺䝪䝗䝟 ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅ 385 䛻䛚䛔䛶 CK䠄CPK䠅䛾ୖ᪼䠄4.8䠂䠅䚸 LDH 䛾ୖ᪼䠄4.7䠂䠅䚸Al-P 䛾ୖ᪼䠄2.9䠂䠅䛷䛒䛳䛯䠄䜶䝣䝢䞊㘄 2.5 ᢎㄆ䠅7䡚13䠅䚹 䜎䛯䚸⏝ᡂ⦼ㄪᰝ䛻䛚䛔䛶䚸䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝ᝈ⪅ 4,692 ୰ 957 䠄20.4䠂䠅䛻స⏝䛜ㄆ䜑䜙䜜䛯䚹䛺స⏝䛿ᗁぬ䠄4.8䠂䠅䚸ᝏᚰ䠄3.1䠂䠅䚸䝆䝇䜻䝛䝆䜰 䠄2.3䠂䠅䚸䜑䜎䛔䠄1.6䠂䠅䚸㣗ḧ䠄1.0䠂䠅䛷䛒䛳䛯䠄䜶䝣䝢䞊㘄 2.5 ᑂᰝ⤊䠅䚹 䛥䜙䛻䚸䝺䝪䝗䝟ྵ᭷〇㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯⮫ᗋヨ㦂䛻䛚䛔䛶䚸327 ୰ 132 䠄40.4䠂䠅䛻స⏝䛜ㄆ䜑䜙䜜䛯䚹䛺స⏝䛿౽⛎䠄5.2䠂䠅䚸╀䠄3.7䠂䠅䚸㧗⾑ᅽ 䠄3.1䠂䠅䚸CK䠄CPK䠅ୖ᪼䠄2.4䠂䠅䚸╀Ẽ䠄2.1䠂䠅䛷䛒䛳䛯䠄䜶䝣䝢䞊OD 㘄 2.5 ຠ⬟㏣ຍᢎㄆ 䠅14䡚16䠅䚹 (2) 㔜䛺స⏝䛸ึᮇ≧ 1) ᗁぬ䠄4.8䠂䠅䚸ዶ䠄1.0䠂䠅䚸㘒䠄0.2䠂䠅䚸䛫䜣ዶ䠄0.4䠂䠅 ᗁぬ䚸ዶ䚸㘒䚸䛫䜣ዶ䛜䛒䜙䜟䜜䜛䛣䛸䛜䛒䜛䛾䛷䚸䛣䛾䜘䛖䛺≧䛜䛒䜙䜟䜜䛯ሙྜ䛻 䛿䚸ῶ㔞䚸ఇ⸆ཪ䛿ᢞ䜢୰Ṇ䛩䜛䛺䛹㐺ษ䛺ฎ⨨䜢⾜䛖䛣䛸䚹 2) ⊃ᚰ䠄㢖ᗘ᫂䠅 ⊃ᚰ䛾Ⓨ⌧ཪ䛿ቑᝏ䛜ሗ࿌䛥䜜䛶䛔䜛䛾䛷䚸⊃ᚰᝈ⪅䛷䛿ᚰ㟁ᅗ䜢䝰䝙䝍䞊䛩䜛䛺 䛹䚸≉䛻ὀព䛩䜛䛣䛸䚹 3) ᝏᛶೃ⩌䠄0.1䠂ᮍ‶䠅 ᮏ䛾ᛴ⃭䛺ῶ㔞ཪ䛿୰Ṇ䛻䜘䜚䚸㧗⇕䚸ព㆑㞀ᐖ䚸㧗ᗘ䛾➽◳┤䚸㝶ព㐠ື䚸⾑Ύ CK䠄CPK䠅ୖ᪼➼䛜䛒䜙䜟䜜䜛䛣䛸䛜䛒䜛䚹䛣䛾䜘䛖䛺ሙྜ䛻䛿䚸ᢞᚋ䚸ῶ䛩䜛䛸䛸䜒 䛻䚸య෭༷䚸Ỉศ⿵⤥➼䛾㐺ษ䛺ฎ⨨䜢⾜䛖䛣䛸䚹䛺䛚䚸ᢞ⥅⥆୰䛻ྠᵝ䛾≧䛜䛒䜙䜟 䜜䜛䛣䛸䛜䛒䜛䚹 4) ప⾑⢾䠄㢖ᗘ᫂䠅 ప⾑⢾䛜䛒䜙䜟䜜䜛䛣䛸䛜䛒䜛䛾䛷䚸ప⾑⢾≧䠄ព㆑㞀ᐖ䚸᫃╧➼䠅䛜䛒䜙䜟䜜䛯ሙྜ䛻 䛿䚸ᢞ䜢୰Ṇ䛩䜛䛺䛹㐺ษ䛺ฎ⨨䜢⾜䛖䛣䛸䚹 5) ⫶₽⒆䠄0.1䠂䠅 ⫶₽⒆䛜䛒䜙䜟䜜䜛䛣䛸䛜䛒䜛䛾䛷䚸䛣䛾䜘䛖䛺ሙྜ䛻䛿䚸ᢞ䜢୰Ṇ䛩䜛䛺䛹㐺ษ䛺ฎ⨨䜢 ⾜䛖䛣䛸䚹 34 (3) 䛭䛾䛾స⏝ ኴᏐ䛾స⏝䛻䛴䛔䛶䛿䛭䜜䛮䜜䛾ὀ䠅䛻䜘䜛䛣䛸䚹 0.1䡚5䠂ᮍ‶ 0.1䠂ᮍ‶ 㝶ព㐠ື䚸⯆ዧ䚸⢭⚄≧䚸䝆䝇䝖 䝙 䜰䠄➽⥭ᙇ␗ᖖ䠅䚸ᵓ㡢㞀ᐖ䚸Ṍ⾜ ␗ᖖ䚸 Ᏻ䚸䜑䜎䛔䞉䜅䜙䛴䛝䚸㢌③䞉 㢌㔜ឤ䚸╀䚸╀Ẽ䚸య䛾䛣䜟䜀䜚䚸䛧 䜃䜜䚸ከክ䚸䛖䛴≧䚸ព㆑䝺䝧䝹䛾 పୗ ⥭ᙇపୗ䚸ᚔᚉⒷ䚸䜰䜹䝅䝆䜰䚸グ᠈ 㞀ᐖ䚸㌄䚸䛽䛤䛸䚸㐠ືపୗ䚸ᝏክ ᾘჾ ᝏᚰ䞉ྤ䚸㣗ḧ䚸ཱྀῬ䚸⫶③䞉 ⭡③䚸౽⛎䚸ୗ⑩䚸ᾘⰋ 㯞⑷ᛶ䜲䝺䜴䝇䚸⫶⭠㞀ᐖ䚸䜲䝺䜴䝇 ᚠ⎔ჾ ㉳❧ᛶప⾑ᅽ䚸ື䚸ప⾑ᅽ䚸㧗⾑ ᅽ䚸ᩚ⬦ ᚰ㟁ᅗ␗ᖖ䚸⾑ᅽኚື䚸䛖䛳⾑ᛶᚰ ⫢⮚ ⫢ ᶵ ⬟ 㞀 ᐖ 䠄 AST 䠄 GOT 䠅 䚸 ALT 䠄GPT䠅䛾ୖ᪼䠅 ⢭⚄⚄⤒⣔ 㐣ᩄ ὀ 3) ὀ 2) Ⓨ⑈ Ἢᒀჾ ⾑ᾮ ᒀᅔ㞴 ⓑ⾑⌫ῶᑡ ⓶ ከᙧ⣚ᩬ䚸⣚ᩬ ║ ど㔝⊃✽ 䛭䛾 ᾋ⭘䚸⬚③䠄⬚㒊ᛌឤ䠅䚸ᛰឤ䚸 䜋䛶䜚䞉䛾䜌䛫䚸ぬ␗ᖖ䚸ከờ䚸Ẽ ศⰋ䚸⑂ປឤ䚸⾑Ύ CK(CPK)ୖ ᪼䚸➽㦵᱁◳┤䚸⭜③ Ⓨ⇕䚸ᝏᐮ䚸య㔜ῶᑡ䚸ぬపୗ䚸⯉ 䛾㐪ឤ䚸ពḧపୗ䚸➽ᨥ⦰䚸㢁㒊 ③䚸ᅄ⫥③䚸↓ຊ䚸≧ែᝏ ὀ2䠅 䛣䛾䜘䛖䛺≧䛜䛒䜙䜟䜜䛯ሙྜ䛻䛿䚸ῶ㔞ཪ䛿ఇ⸆䛩䜛䛺䛹㐺ษ䛺ฎ⨨䜢⾜䛖䛣䛸䚹 ὀ3䠅 䛣䛾䜘䛖䛺ሙྜ䛻䛿ᢞ䜢୰Ṇ䛩䜛䛣䛸䚹 Ⓨ⌧㢖ᗘ䛿䜶䝣䝢䞊㘄 2.5 䛾䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯⮫ᗋヨ 㦂䚸䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝ᝈ⪅䜢ᑐ㇟䛸䛧䛯⏝ᡂ⦼ㄪᰝཬ䜃䜶䝣䝢䞊OD 㘄 2.5 䛾䝺䝪䝗䝟ྵ ᭷〇㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯⮫ᗋヨ㦂䛾⤖ᯝ䜢ྜ䜟䛫䛶⟬ฟ䛧䛯䚹 35 (4) 㡯┠ูస⏝Ⓨ⌧㢖ᗘཬ䜃⮫ᗋ᳨ᰝ್␗ᖖ୍ぴ 1) 䜶䝣䝢䞊㘄 2.5 ᢎㄆ䛾స⏝Ⓨ⌧≧ἣ 7䡚13) స⏝Ⓨ⌧⋡ ㄪᰝᩘ స⏝Ⓨ⌧ᩘ స⏝Ⓨ⌧௳ᩘ స⏝Ⓨ⌧⋡ 䝺䝪䝗䝟ే⏝ 䝺䝪䝗䝟㠀ే⏝ ྜィ 387 157 290 ௳ 40.6䠂 101 20 31 ௳ 19.8䠂 488 177 321 ௳ 36.3䠂 㡯┠ูస⏝Ⓨ⌧㢖ᗘ ⢭⚄⚄⤒⣔ ᾘჾ⣔ ᚠ⎔ჾ⣔ 㐣ᩄ ⫢⮚ ⾑ᾮ Ἢᒀჾ⣔ ║ స⏝䛾✀㢮 䝆䝇䜻䝛䝆䜰 ᗁぬ 䜑䜎䛔䞉䜅䜙䛴䛝 㢌③䞉㢌㔜ឤ ዶ ⯆ዧ 㘒 ⢭⚄≧ ╀ 䝆䝇䝖䝙䜰 ╀Ẽ య䛾䛣䜟䜀䜚 䛧䜃䜜 䛫䜣ዶ ከክ ᵓ㡢㞀ᐖ ⥭ᙇపୗ Ᏻ 䛖䛴≧ Ṍ⾜␗ᖖ ᝏᚰ䞉ྤ 㣗ḧ ཱྀῬ䠄ឤ䠅 ⫶③䞉⭡③ ౽⛎ ୗ⑩ ㉳❧ᛶప⾑ᅽ ື 㧗⾑ᅽ ᩚ⬦ ᚰ㟁ᅗ␗ᖖ ప⾑ᅽ Ⓨ⑈ ⫢ᶵ⬟㞀ᐖ ⓑ⾑⌫ῶᑡഴྥ ᒀᅔ㞴 ど㔝⊃✽ 䝺䝪䝗䝟ే⏝ 30 䠄7.8䠅 28 䠄7.2䠅 27 䠄7.0䠅 17 䠄4.4䠅 11 䠄2.8䠅 4 䠄1.0䠅 4 䠄1.0䠅 4 䠄1.0䠅 3 䠄0.8䠅 3 䠄0.8䠅 3 䠄0.8䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 36 䠄9.3䠅 28 䠄7.2䠅 13 䠄3.4䠅 6 䠄1.6䠅 3 䠄0.8䠅 2 䠄0.5䠅 16 䠄4.1䠅 5 䠄1.3䠅 2 䠄0.5䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 3 䠄0.8䠅 1 䠄0.3䠅 1 䠄0.3䠅 0 䠄0.0䠅 0 䠄0.0䠅 䝺䝪䝗䝟㠀ే⏝ 2 䠄2.0䠅 4 䠄4.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 1 䠄1.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 2 䠄2.0䠅 2 䠄2.0䠅 2 䠄2.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 1 䠄1.0䠅 3 䠄3.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 2 䠄2.0䠅 0 䠄0.0䠅 1 䠄1.0䠅 1 䠄1.0䠅 32 32 28 17 11 4 4 4 4 3 3 2 2 1 1 1 1 1 1 1 38 30 15 7 3 3 19 6 2 1 1 1 3 3 1 1 1 ྜィ 䠄6.6䠅 䠄6.6䠅 䠄5.7䠅 䠄3.5䠅 䠄2.3䠅 䠄0.8䠅 䠄0.8䠅 䠄0.8䠅 䠄0.8䠅 䠄0.6䠅 䠄0.6䠅 䠄0.4䠅 䠄0.4䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄7.8䠅 䠄6.1䠅 䠄3.1䠅 䠄1.4䠅 䠄0.6䠅 䠄0.6䠅 䠄3.9䠅 䠄1.2䠅 䠄0.4䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.6䠅 䠄0.6䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 ௳ᩘ䠄䠂䠅 36 㡯┠ูస⏝Ⓨ⌧㢖ᗘ䠄䛴䛵䛝䠅 䛭䛾 స⏝䛾✀㢮 ᾋ⭘ ⬚③䠄⬚㒊ᛌឤ䠅 ᛰឤ 䜋䛶䜚 ぬ␗ᖖ ከờ ẼศⰋ ⑂ປឤ Ⓨ⇕ 䛾䜌䛫 ⾑Ύ CK(CPK)ୖ᪼ ᝏᐮ య㔜ῶᑡ ⮬ぬ≧ᝏ ぬపୗ ⯉䛾㐪ឤ ⭜③ ពḧపୗ 䝺䝪䝗䝟ే⏝ 5 䠄1.3䠅 4 䠄1.0䠅 3 䠄0.8䠅 2 䠄0.5䠅 2 䠄0.5䠅 2 䠄0.5䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 1 䠄0.3䠅 0 䠄0.0䠅 0 䠄0.0䠅 䝺䝪䝗䝟㠀ే⏝ 1 䠄1.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 1 䠄1.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 0 䠄0.0䠅 1 䠄1.0䠅 1 䠄1.0䠅 6 5 3 3 2 2 1 1 1 1 1 1 1 1 1 1 1 1 ྜィ 䠄1.2䠅 䠄1.0䠅 䠄0.6䠅 䠄0.6䠅 䠄0.4䠅 䠄0.4䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 䠄0.2䠅 ௳ᩘ䠄䠂䠅 ⮫ᗋ᳨ᰝ್␗ᖖ୍ぴ ᳨ᰝ㡯┠ ⾑ᾮᏛⓗ ᳨ᰝ ⾑Ύ⏕Ꮫⓗ ᳨ᰝ ᒀᐃᛶ᳨ᰝ ㉥⾑⌫ᩘ ⓑ⾑⌫ᩘ 䝦䝰䜾䝻䝡䞁 䝦䝬䝖䜽䝸䝑䝖 ⾑ᑠᯈᩘ GOT GPT Al-P LDH 䝡䝸䝹䝡䞁 䃒-GTP BUN 䜽䝺䜰䝏䝙䞁 ᒀ㓟 ⥲䝁䝺䝇䝔䝻䞊䝹 ⾑⢾ CK(CPK) Na K Cl ⺮ⓑ ⢾ ₯⾑ ᐇ ᩘ 378 379 376 375 365 382 384 374 379 374 178 379 377 257 375 86 84 365 364 367 344 342 300 37 ␗ᖖኚື௳ᩘ䠄䠂䠅 ᅉᯝ㛵ಀ䛒䜚 ᅉᯝ㛵ಀ᫂ ྜィ 2 䠄0.5䠅 5 䠄1.3䠅 7 䠄1.9䠅 1 䠄0.3䠅 6 䠄1.6䠅 7 䠄1.8䠅 1 䠄0.3䠅 5 䠄1.3䠅 6 䠄1.6䠅 1 䠄0.3䠅 7 䠄1.9䠅 8 䠄2.1䠅 2 䠄0.5䠅 1 䠄0.3䠅 3 䠄0.8䠅 3 䠄0.8䠅 4 䠄1.0䠅 7 䠄1.8䠅 1 䠄0.3䠅 1 䠄0.3䠅 2 䠄0.5䠅 4 䠄1.1䠅 7 䠄1.9䠅 11 䠄2.9䠅 9 䠄2.4䠅 9 䠄2.4䠅 18 䠄4.7䠅 0 䠄0.0䠅 4 䠄1.1䠅 4 䠄1.1䠅 1 䠄0.6䠅 0 䠄0.0䠅 1 䠄0.6䠅 3 䠄0.8䠅 3 䠄0.8䠅 6 䠄1.6䠅 1 䠄0.3䠅 3 䠄0.8䠅 4 䠄1.1䠅 3 䠄1.2䠅 0 䠄0.0䠅 3 䠄1.2䠅 1 䠄0.3䠅 3 䠄0.8䠅 4 䠄1.0䠅 0 䠄0.0䠅 2 䠄2.3䠅 2 䠄2.3䠅 3 䠄3.6䠅 1 䠄1.2䠅 4 䠄4.8䠅 0 䠄0.0䠅 1 䠄0.3䠅 1 䠄0.3䠅 0 䠄0.0䠅 6 䠄1.6䠅 6 䠄1.6䠅 0 䠄0.0䠅 9 䠄2.5䠅 9 䠄2.5䠅 2 䠄0.6䠅 5 䠄1.5䠅 7 䠄2.0䠅 0 䠄0.0䠅 1 䠄0.3䠅 1 䠄0.3䠅 0 䠄0.0䠅 3 䠄1.0䠅 3 䠄1.0䠅 2) 䜶䝣䝢䞊㘄 2.5 ᑂᰝ⤊䠄⏝ᡂ⦼ㄪᰝ䠅䛾స⏝Ⓨ⌧≧ἣ స⏝Ⓨ⌧⋡ ⏝ᡂ⦼ㄪᰝ ᑐ㇟ᩘ స⏝Ⓨ⌧ᩘ స⏝Ⓨ⌧௳ᩘ స⏝Ⓨ⌧⋡ 4692 957 1266 ௳ 20.4䠂 ჾᐁูస⏝Ⓨ⌧㢖ᗘ ჾᐁศ㢮 ௳ᩘ䠄䠂䠅 ჾᐁศ㢮 ឤᰁ䛚䜘䜃ᐤ⏕ 1䠄0.02䠅 ⾑⟶㞀ᐖ Ⰻᛶ䚸ᝏᛶ䛚䜘䜃ヲ⣽᫂䛾᪂⏕≀ 1䠄0.02䠅 ྾ჾ䚸⬚㒌䛚䜘䜃⦪㝸㞀ᐖ 䠄ᄞ⬊䛚䜘䜃䝫䝸䞊䝥䜢ྵ䜐䠅 ⾑ᾮ䛚䜘䜃䝸䞁䝟⣔㞀ᐖ ௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ 3䠄0.06䠅 50䠄1.07䠅 ⢭⚄㞀ᐖ 320䠄6.82䠅 ⚄⤒⣔㞀ᐖ 297䠄6.33䠅 ║㞀ᐖ 5䠄0.11䠅 ⪥䛚䜘䜃㏞㊰㞀ᐖ 3䠄0.06䠅 ᚰ⮚㞀ᐖ 13䠄0.28䠅 ⫶⭠㞀ᐖ ௳ᩘ䠄䠂䠅 45䠄0.96䠅 6䠄0.13䠅 241䠄5.14䠅 ⫢⫹㐨⣔㞀ᐖ 19䠄0.40䠅 ⓶䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ 27䠄0.58䠅 ➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ 26䠄0.55䠅 ⭈䛚䜘䜃ᒀ㊰㞀ᐖ 3䠄0.06䠅 ୍⯡䞉㌟㞀ᐖ䛚䜘䜃ᢞ㒊䛾≧ែ 58䠄1.24䠅 ⮫ᗋ᳨ᰝ 17䠄0.36䠅 യᐖ䚸୰ẘ䛚䜘䜃ฎ⨨ྜే 7䠄0.15䠅 㡯┠ูస⏝Ⓨ⌧㢖ᗘ స⏝䛾✀㢮 ௳ᩘ䠄䠂䠅 ឤᰁ䛚䜘䜃ᐤ⏕ ᆶ⅖ 1䠄0.02䠅 䠄ᄞ⬊䛚䜘䜃䝫䝸䞊䝥䜢ྵ䜐䠅 1䠄0.02䠅 ⾑ᾮ䛚䜘䜃䝸䞁䝟⣔㞀ᐖ ⓑ⾑⌫ῶᑡ ዲ㓟⌫ቑຍ 2䠄0.04䠅 1䠄0.02䠅 ௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ 㣗ḧῶ㏥ 䜰䝹䝁䞊䝹⪏ᛶ 㧗ᒀ㓟⾑ ప䝘䝖䝸䜴䝮⾑ 㧗⬡⾑ ௳ᩘ䠄䠂䠅 ⢭⚄㞀ᐖ Ⰻᛶ䚸ᝏᛶ䛚䜘䜃ヲ⣽᫂䛾᪂⏕≀ ⫶⒴ స⏝䛾✀㢮 47䠄1.00䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 38 ᗁぬ ዶ ╀ ⢭⚄≧ ㆛ዶ ⃭㉺ ␗ᖖ䛺ክ ᝏክ ᚔᚉⒷ 䛖䛴 㘒≧ែ ⴠ䛱╔䛝䛾䛺䛥 ↓Ⅽ ␗ᖖ⾜ື ኻぢᙜ㆑ 㘒ぬ ่⃭᫆ᛶ 䝸䝡䝗䞊ஹ㐍 ㌄ 225䠄4.80䠅 46䠄0.98䠅 23䠄0.49䠅 21䠄0.45䠅 18䠄0.38䠅 15䠄0.32䠅 5䠄0.11䠅 5䠄0.11䠅 5䠄0.11䠅 4䠄0.09䠅 3䠄0.06䠅 3䠄0.06䠅 3䠄0.06䠅 3䠄0.06䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 㡯┠ูస⏝Ⓨ⌧㢖ᗘ䠄䛴䛵䛝䠅 స⏝䛾✀㢮 2䠄0.04䠅 2䠄0.04䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 ⚄⤒⣔㞀ᐖ 䝆䝇䜻䝛䝆䜰 ᾋືᛶ䜑䜎䛔 ഴ╀ 㢌③ ព㆑ኚᐜ≧ែ యᛶ䜑䜎䛔 ᡓ 䝆䝇䝖䝙䜰 ぬ␗ᖖ ᵓ㡢㞀ᐖ ឤぬ㕌㯞 グ᠈㞀ᐖ ᝏᛶೃ⩌ 䜰䜹䝅䝆䜰 㐠ືపୗ ぬᾘኻ ⮬ᚊ⚄⤒ኻㄪ ⅎ⇕ឤ ⬻ฟ⾑ ②ᨥ ㄆ▱ ὀពຊ㞀ᐖ ➽⥭ᙇஹ㐍 ➽⥭ᙇపୗ ព㆑ᾘኻ 䝯䞊䝆ೃ⩌ 㘒ឤぬ 䝟䞊䜻䞁䝋䝙䝈䝮 䝉䝻䝖䝙䞁ೃ⩌ ど㔝Ḟᦆ ᖹ⾮㞀ᐖ 䛩䛟䜏⌧㇟ ௳ᩘ䠄䠂䠅 ⪥䛚䜘䜃㏞㊰㞀ᐖ ⢭⚄㞀ᐖ䠄䛴䛵䛝䠅 䛽䛤䛸 ᢚ䛖䛴≧ Ᏻ ⚄⤒㐣ᩄ ឤᏳᐃ స⏝䛾✀㢮 ௳ᩘ䠄䠂䠅 108䠄2.30䠅 73䠄1.56䠅 32䠄0.68䠅 28䠄0.60䠅 10䠄0.21䠅 8䠄0.17䠅 8䠄0.17䠅 7䠄0.15䠅 6䠄0.13䠅 5䠄0.11䠅 5䠄0.11䠅 3䠄0.06䠅 3䠄0.06䠅 2䠄0.04䠅 2䠄0.04䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 ║㞀ᐖ ║⢭⑂ປ 1䠄0.02䠅 ║▛②ᨥ ⥳ෆ㞀 ගど 㯤ど 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 39 ⪥③ 2䠄0.04䠅 ⫈ຊపୗ 1䠄0.02䠅 ᚰ⮚㞀ᐖ ື ᩚ⬦ ᚰᡣ⣽ື 䝏䜰䝜䞊䝊 10䠄0.21䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 ⾑⟶㞀ᐖ ㉳❧ᛶప⾑ᅽ 䜋䛶䜚 ప⾑ᅽ ⾑ᅽኚື 㧗⾑ᅽ ᮎᲈ෭ឤ 27䠄0.58䠅 7䠄0.15䠅 5䠄0.11䠅 4䠄0.09䠅 1䠄0.02䠅 1䠄0.02䠅 ྾ჾ䚸⬚㒌䛚䜘䜃⦪㝸㞀ᐖ ྾❓㏕ 2䠄0.04䠅 ᜥワ䜎䜚ឤ Ⓨኌ㞀ᐖ ྾ᅔ㞴 ⑱㈓␃ 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 ⫶⭠㞀ᐖ ᝏᚰ ⭡㒊ᛌឤ ྤ ౽⛎ ཱྀෆ⇱ ୖ⭡㒊③ ୗ⑩ ᾘⰋ ⫶₽⒆ ⭡③ ὶᾝ㐣ከ ⫶⭠㞀ᐖ Ẽ⮯ ⯉③ 㯞⑷ᛶ䜲䝺䜴䝇 ཱྀ⭍ෆᛌឤ ṑ䛾㞀ᐖ ᚰ❐㒊ᛌឤ ཱྀ䛾㘒ឤぬ 147䠄3.13䠅 23䠄0.49䠅 20䠄0.43䠅 16䠄0.34䠅 13䠄0.28䠅 10䠄0.21䠅 8䠄0.17䠅 5䠄0.11䠅 4䠄0.09䠅 3䠄0.06䠅 3䠄0.06䠅 2䠄0.04䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 㡯┠ูస⏝Ⓨ⌧㢖ᗘ䠄䛴䛵䛝䠅 స⏝䛾✀㢮 ௳ᩘ䠄䠂䠅 ⫢⫹㐨⣔㞀ᐖ ⫢ᶵ⬟␗ᖖ ⫹ᄞ⅖ ⫹▼ ከờ 䛭䛖 ⸆⑈ ⬺ẟ ⣚ᩬ ከᙧ⣚ᩬ ᐷờ ⶼ㯞⑈ ୰ẘᛶ⓶⑈ Ⰽ⣲ỿ╔㞀ᐖ ௳ᩘ䠄䠂䠅 ୍⯡䞉㌟㞀ᐖ䛚䜘䜃ᢞ㒊䛾≧ែ 18䠄0.38䠅 1䠄0.02䠅 1䠄0.02䠅 ⓶䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ Ⓨ⑈ స⏝䛾✀㢮 10䠄0.21䠅 6䠄0.13䠅 3䠄0.06䠅 2䠄0.04䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 Ṍ⾜㞀ᐖ 9䠄0.19䠅 ⬚③ ᛰឤ ␗ᖖឤ Ṛஸ ⑂ປ ↓ຊ ᮎᲈᛶᾋ⭘ ⬚㒊ᛌឤ ≧ែᝏ Ⓨ⇕ ✺↛Ṛ ᝏᐮ 䜃䛟䜃䛟ឤ ᾋ⭘ 8䠄0.17䠅 8䠄0.17䠅 6䠄0.13䠅 5䠄0.11䠅 5䠄0.11䠅 3䠄0.06䠅 3䠄0.06䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 ⮫ᗋ᳨ᰝ ➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ ➽ᅛ⦰ 7䠄0.15䠅 ⾑୰ CK䠄CPK䠅ቑຍ 6䠄0.13䠅 ➽㦵᱁◳┤ ⫼㒊③ ➽ᨥ⦰ ➽㦵᱁③ ➽⫗③ ᅄ⫥③ ➽ຊపୗ ጼໃ␗ᖖ 6䠄0.13䠅 4䠄0.09䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 2䠄0.04䠅 1䠄0.02䠅 1䠄0.02䠅 ⾑୰ᒀ⣲ቑຍ ALT䠄GPT䠅ቑຍ 䜰䝭䝷䞊䝊ቑຍ AST䠄GOT䠅ቑຍ ⾑୰䝁䝺䝇䝔䝻䞊䝹ቑຍ ⾑୰䝁䝸䞁䜶䝇䝔䝷䞊䝊ቑຍ ⾑୰ LDH ቑຍ ⾑ᅽୖ᪼ ᚰ㟁ᅗ ST 㒊ศୖ᪼ 䃒-GT ቑຍ 䝦䝰䜾䝻䝡䞁ῶᑡ పẚ㔜䝸䝫⺮ⓑቑຍ య㔜ῶᑡ 3䠄0.06䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 1䠄0.02䠅 ⭈䛚䜘䜃ᒀ㊰㞀ᐖ ᒀᅔ㞴 2䠄0.04䠅 㢖ᒀ 1䠄0.02䠅 യᐖ䚸୰ẘ䛚䜘䜃ฎ⨨ྜే ㌿ಽ 6䠄0.13䠅 㦵ᢡ 1䠄0.02䠅 ⾲୰䛾స⏝➼䛾ྡ⛠䛿䛂ICH ᅜ㝿་⸆⏝ㄒ㞟᪥ᮏㄒ∧䠄MedDRA/J䠅Ver.17.0䛃䛾⏝ㄒ䜢⏝䚹 40 3) 䜶䝣䝢䞊OD 㘄 2.5 ຠ⬟㏣ຍᢎㄆ䛾స⏝Ⓨ⌧≧ἣ 14~16) స⏝Ⓨ⌧⋡ ᑐ㇟ᩘ 327 స⏝Ⓨ⌧ᩘ 132 స⏝Ⓨ⌧⋡ 40.4䠂 ჾᐁูస⏝Ⓨ⌧㢖ᗘ ௳ᩘ䠄䠂䠅 ჾᐁศ㢮 ឤᰁ䛚䜘䜃ᐤ⏕ 2䠄0.6䠅 ྾ჾ䚸⬚㒌䛚䜘䜃⦪㝸㞀ᐖ ⾑ᾮ䛚䜘䜃䝸䞁䝟⣔㞀ᐖ 1䠄0.3䠅 ⫶⭠㞀ᐖ ච⣔㞀ᐖ 2䠄0.6䠅 ⫢⫹㐨⣔㞀ᐖ 8䠄2.4䠅 ෆศἪ㞀ᐖ 1䠄0.3䠅 ⓶䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ 9䠄2.8䠅 ௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ 4䠄1.2䠅 ➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ 15䠄4.6䠅 ჾᐁศ㢮 ௳ᩘ䠄䠂䠅 2䠄0.6䠅 37䠄11.3䠅 ⢭⚄㞀ᐖ 19䠄5.8䠅 ⭈䛚䜘䜃ᒀ㊰㞀ᐖ 7䠄2.1䠅 ⚄⤒⣔㞀ᐖ 24䠄7.3䠅 ⏕Ṫ⣔䛚䜘䜃ஙᡣ㞀ᐖ 1䠄0.3䠅 9䠄2.8䠅 ║㞀ᐖ 3䠄0.9䠅 ୍⯡䞉㌟㞀ᐖ䛚䜘䜃ᢞ㒊䛾≧ែ ⪥䛚䜘䜃㏞㊰㞀ᐖ 2䠄0.6䠅 ⮫ᗋ᳨ᰝ ᚰ⮚㞀ᐖ 8䠄2.4䠅 യᐖ䚸୰ẘ䛚䜘䜃ฎ⨨ྜే ⾑⟶㞀ᐖ 15䠄4.6䠅 42䠄12.8䠅 6䠄1.8䠅 㡯┠ูస⏝Ⓨ⌧㢖ᗘ స⏝䛾✀㢮 స⏝䛾✀㢮 ௳ᩘ䠄䠂䠅 ⚄⤒⣔㞀ᐖ ឤᰁ䛚䜘䜃ᐤ⏕ ⭤⬔⅖ 㰯ဗ㢌⅖ 1䠄0.3䠅 1䠄0.3䠅 ഴ╀ ᾋືᛶ䜑䜎䛔 యᛶ䜑䜎䛔 㢌③ ↓ື ὀពຊ㞀ᐖ ぬ␗ᖖ 䝆䝇䝖䝙䜰 ព㆑ᾘኻ ⚄⤒③ Ⴅぬ㘒ㄗ ⫘㛫⚄⤒③ ⾑ᾮ䛚䜘䜃䝸䞁䝟⣔㞀ᐖ ㈋⾑ 1䠄0.3䠅 ච⣔㞀ᐖ Ꮨ⠇ᛶ䜰䝺䝹䜼䞊 2䠄0.6䠅 ෆศἪ㞀ᐖ ⏥≧⭢⭘⒗ 1䠄0.3䠅 ௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ 㣗ḧῶ㏥ ⢾ᒀ ప䝘䝖䝸䜴䝮⾑ 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 7䠄2.1䠅 4䠄1.2䠅 4䠄1.2䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ║㞀ᐖ ⢭⚄㞀ᐖ ╀ ᗁぬ ᗁど 䛖䛴 ╧╀㞀ᐖ ␗ᖖ⾜ື ௳ᩘ䠄䠂䠅 ║䛾␗ᖖឤ 㛝㍤ᬯⅬ ◪Ꮚయᾋ㐟≀ 12䠄3.7䠅 3䠄0.9䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ⪥䛚䜘䜃㏞㊰㞀ᐖ ⪥㬆 ᅇ㌿ᛶ䜑䜎䛔 41 1䠄0.3䠅 1䠄0.3䠅 㡯┠ูస⏝Ⓨ⌧㢖ᗘ䠄䛴䛵䛝䠅 స⏝䛾✀㢮 ௳ᩘ䠄䠂䠅 స⏝䛾✀㢮 ᚰ⮚㞀ᐖ ᚰᐊᛶᮇእ⦰ ᚰᡣ⣽ື ᚰᐊෆఏᑟ㞀ᐖ ື Ὕᛶᩚ⬦ 㢖⬦ ⓶䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ 3䠄0.9䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ⾑⟶㞀ᐖ 㧗⾑ᅽ ㉳❧ᛶప⾑ᅽ 䜋䛶䜚 10䠄3.1䠅 4䠄1.2䠅 2䠄0.6䠅 2䠄0.6䠅 1䠄0.3䠅 17䠄5.2䠅 4䠄1.2䠅 4䠄1.2䠅 4䠄1.2䠅 4䠄1.2䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ⬺ẟ 1䠄0.3䠅 ⓶⅖ 1䠄0.3䠅 䜰䝖䝢䞊ᛶ⓶⅖ 1䠄0.3䠅 ‵⑈ 1䠄0.3䠅 ㈌ᖯ≧‵⑈ 1䠄0.3䠅 䛭䛖 1䠄0.3䠅 ⶼ㯞⑈ 1䠄0.3䠅 6䠄1.8䠅 3䠄0.9䠅 2䠄0.6䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ⭈䛚䜘䜃ᒀ㊰㞀ᐖ ⥭ᙇᛶ⭤⬔ ᒀ㊰⤖▼ ⾑ᒀ 㢖ᒀ ⺮ⓑᒀ ⭈ᶵ⬟㞀ᐖ 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ⏕Ṫ⣔䛚䜘䜃ஙᡣ㞀ᐖ Ⰻᛶ๓❧⭢⫧ ⫢⫹㐨⣔㞀ᐖ ⫢㞀ᐖ ⫢ᶵ⬟␗ᖖ ᛴᛶ⫹ᄞ⅖ ⫹▼ 㧗䝡䝸䝹䝡䞁⾑ 2䠄0.6䠅 ⫼㒊③ ➽⫗③ ኚᙧᛶ㛵⠇ ᅄ⫥③ 㛵⠇③ ᾮໟ⅖ ➽②⦰ ጼໃ␗ᖖ ➽㦵᱁◳┤ ⫶⭠㞀ᐖ ౽⛎ ⭡㒊ᛌឤ ୗ⑩ ᝏᚰ ྤ ⫶₽⒆ ⭡③ ୖ⭡㒊③ ཱྀ၁⅖ ᾘⰋ ฟ⾑ᛶ⫶₽⒆ ⫶⅖ 㐣ᩄᛶ⭠ೃ⩌ ὶᾝ㐣ከ Ⓨ⑈ ➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ ྾ჾ䚸⬚㒌䛚䜘䜃⦪㝸㞀ᐖ ၻ⑱ቑຍ တႿ ௳ᩘ䠄䠂䠅 1䠄0.3䠅 ୍⯡䞉㌟㞀ᐖ䛚䜘䜃ᢞ㒊䛾≧ែ 4䠄1.2䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 ཱྀῬ ᾋ⭘ ⬚㒊ᛌឤ ᛰឤ ✺↛Ṛ 42 5䠄1.5䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 㡯┠ูస⏝Ⓨ⌧㢖ᗘ䠄䛴䛵䛝䠅 స⏝䛾✀㢮 ௳ᩘ䠄䠂䠅 ⮫ᗋ᳨ᰝ ⾑୰ CK䠄CPK䠅ቑຍ ⓑ⾑⌫ᩘῶᑡ 䃒-GT ቑຍ ⾑୰ Al-P ቑຍ ᒀ୰䝤䝗䜴⢾㝧ᛶ ⾑୰ᒀ⣲ቑຍ ᒀ୰⺮ⓑ㝧ᛶ ᒀ୰⾑㝧ᛶ 䝸䞁䝟⌫ᩘῶᑡ ALT䠄GPT䠅ቑຍ AST䠄GOT䠅ቑຍ ዲሷᇶ⌫ᩘቑຍ ⾑୰䝡䝸䝹䝡䞁ቑຍ ⾑ᅽୖ᪼ ዲ㓟⌫ᩘቑຍ 䃒-GT ␗ᖖ ༢⌫ᩘቑຍ ዲ୰⌫ᩘῶᑡ ዲ୰⌫ᩘቑຍ య㔜ῶᑡ ⓑ⾑⌫ᩘቑຍ ዲሷᇶ⌫ⓒศ⋡ቑຍ ዲ㓟⌫ⓒศ⋡ῶᑡ ዲ㓟⌫ⓒศ⋡ቑຍ ⫢㓝⣲ୖ᪼ ᒀ୰䜴䝻䝡䝸䝜䞊䝀䞁ቑຍ 8䠄2.4䠅 6䠄1.8䠅 5䠄1.5䠅 5䠄1.5䠅 4䠄1.2䠅 3䠄0.9䠅 3䠄0.9䠅 2䠄0.6䠅 2䠄0.6䠅 2䠄0.6䠅 2䠄0.6䠅 2䠄0.6䠅 2䠄0.6䠅 2䠄0.6䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 1䠄0.3䠅 യᐖ䚸୰ẘ䛚䜘䜃ฎ⨨ྜే ㌿ಽ യ ⒔ 3䠄0.9䠅 2䠄0.6䠅 1䠄0.3䠅 ⾲୰䛾స⏝➼䛾ྡ⛠䛿䛂ICH ᅜ㝿་⸆⏝ㄒ㞟᪥ᮏㄒ∧䠄MedDRA/J䠅Ver.17.0䛃䛾⏝ㄒ䜢⏝䚹 43 (5) ᇶ♏ᝈ䚸ྜే䚸㔜ᗘཬ䜃ᡭ⾡䛾᭷↓➼⫼ᬒู䛾స⏝Ⓨ⌧㢖ᗘ 1) 䜶䝣䝢䞊㘄 2.5 ᢎㄆ ᝈ⪅⫼ᬒ ᑐ㇟ᩘ Ⓨ⌧ᩘ Ⓨ⌧⋡䠄䠂䠅 ྜィ 488 177 36.3 ⏨ 229 85 37.1 ዪ 259 92 35.5 65 ṓᮍ‶ 275 99 36.0 65 ṓ௨ୖ 213 78 36.6 3 ᖺᮍ‶ 106 17 16.0 3䍺䚸䠘5 92 32 34.8 5䍺䚸䠘10 163 69 42.3 10 ᖺ௨ୖ 127 59 46.5 䊢ᗘᮍ‶ 173 53 30.6 䊢ᗘ௨ୖ 315 124 39.4 䝺䝪䝗䝟௨እ䛾ᢠ䝟䞊䜻 䛺䛧 87 29 33.3 䞁䝋䞁 䛒䜚 401 148 36.9 ᝈ⪅⫼ᬒ ᑐ㇟ᩘ Ⓨ⌧ᩘ Ⓨ⌧⋡䠄䠂䠅 ྜィ 4692 957 20.4 ⏨ 2145 399 18.6 ዪ 2547 558 21.9 㧗㱋⪅䠷65 ṓ௨ୖ䠹 65 ṓᮍ‶ 1860 336 18.1 65 ṓ௨ୖ 2832 621 21.9 㧗㱋⪅䠷75 ṓ௨ୖ䠹 75 ṓᮍ‶ 3787 758 20.0 75 ṓ௨ୖ 905 199 22.0 3 ᖺᮍ‶ 763 134 17.6 3䍺䚸䠘5 805 134 16.6 5䍺䚸䠘10 1652 334 20.2 10 ᖺ௨ୖ 1294 322 24.9 ᫂ 178 33 18.5 ᛶู 㧗㱋⪅ ⨯ᮇ㛫䠄ᖺ䠅 Yahr 㔜ᗘ 2) 䜶䝣䝢䞊㘄 2.5 ᑂᰝ⤊䠄⏝ᡂ⦼ㄪᰝ䠅 ᛶู ⨯ᮇ㛫䠄ᖺ䠅 Yahr 㔜ᗘ 䊢ᗘᮍ‶ 1089 198 18.2 䊢ᗘ௨ୖ 3597 756 21.0 ᫂ 6 3 50.0 䝺䝪䝗䝟௨እ䛾ᢠ䝟䞊䜻 䛺䛧 613 124 20.2 䞁䝋䞁 䛒䜚 4079 833 20.4 44 3) 䜶䝣䝢䞊OD 㘄 2.5 ຠ⬟㏣ຍᢎㄆ ᝈ⪅⫼ᬒ ᑐ㇟ᩘ Ⓨ⌧ᩘ Ⓨ⌧⋡䠄䠂䠅 ྜィ 327 132 40.4 ⏨ 150 67 44.7 ዪ 177 65 36.7 65 ṓᮍ‶ 150 56 37.3 65 ṓ௨ୖ 177 76 42.9 䊢ᗘᮍ‶ 277 106 38.3 䊢ᗘ௨ୖ 50 26 52.0 ᛶู ᖺ㱋 ὀ 1䠅 Modified Yahr 㔜ᗘ ὀ 2䠅 ὀ 1䠅 ྠពྲྀᚓ ὀ 2䠅 ᢞ㛤ጞ๓᪥ (6) ⸆≀䜰䝺䝹䜼䞊䛻ᑐ䛩䜛ὀពཬ䜃ヨ㦂ἲ 1) ᮏ䛾ᡂศ䛻ᑐ䛧㐣ᩄ䛾᪤ Ṕ䛾䛒䜛ᝈ⪅䛻䛿ᢞ䛧䛺䛔䛣䛸䚹 䠄䛂2䠊⚗ᚷෆᐜ䛸䛭䛾⌮⏤(1)䛃䜢ཧ↷䠅 2) 㐣ᩄ䠄Ⓨ⑈䠅䛜䛒䜙䜟䜜䜛䛣䛸䛜䛒䜛䛾䛷䚸䛣䛾䜘䛖䛺ሙྜ䛻䛿ᢞ䜢୰Ṇ䛩䜛䛣䛸䚹 䠄䛂8䠊స⏝ (3)䛭䛾䛾స⏝䛃䜢ཧ↷䠅 䠕䠊 㧗㱋⪅䜈䛾ᢞ 㧗㱋⪅䜈䛾ᢞ (1) 㧗㱋⪅䛷䛿䚸㉳❧ᛶప⾑ᅽ䛜䛒䜙䜟䜜䜔䛩䛔䛾䛷䚸ቑ㔞䛻䛒䛯䛳䛶䛿䚸⾑ᅽ䛾䝰䝙䝍䝸䞁䜾䜢⾜䛖 䛺䛹䚸ᝈ⪅䛾≧ែ䜢ほᐹ䛧䛺䛜䜙䚸ៅ㔜䛻ᢞ䛩䜛䛣䛸䚹 (2) 䜶䝣䝢䞊㘄 2.5 䛾䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝ᝈ⪅䜢ᑐ㇟䛸䛧䛯ᕷ㈍ᚋㄪᰝ䛷㞟䛧䛯Ᏻ ᛶゎᯒᑐ㇟䛻䛚䛔䛶䚸65 ṓ௨ୖ䛾䛻䛚䛡䜛స⏝Ⓨ⌧⋡䠄㣗ḧ䚸䛫䜣ዶ䚸 ᗁぬ䚸㉳❧ᛶప⾑ᅽ䚸ྤ䚸Ṍ⾜␗ᖖ䠅䛿䚸65 ṓᮍ‶䛾䛻ẚ䜉䛶㧗䛔ഴྥ䛜ㄆ䜑䜙䜜䛶䛔 䜛䚹䜎䛯䚸75 ṓ௨ୖ䛾䛷䛿䚸㣗ḧ䚸ᗁぬ䚸㉳❧ᛶప⾑ᅽ䚸ᝏᚰ䚸Ṍ⾜ᅔ㞴䛾Ⓨ⌧ ⋡䛜䚸75 ṓᮍ‶䛾䛻ẚ䜉䛶㧗䛔ഴྥ䛜ㄆ䜑䜙䜜䛶䛔䜛䚹 (1) 䜶䝣䝢䞊㘄 2.5 ᢎㄆ䜎䛷䛾䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸 䛧䛯⮫ᗋヨ㦂䛻䛚䛔䛶䚸65 ṓ௨ୖཬ䜃 65 ṓᮍ‶䛷ẚ㍑䛧䛯䛸䛣䜝䚸65 ṓ௨ୖ䛾䛷㉳❧ᛶ ప⾑ᅽ䛾Ⓨ⌧㢖ᗘ䛜㧗䛛䛳䛯䛯䜑ᮏ㡯┠䜢タᐃ䛧䛯䚹 (2) 䜶䝣䝢䞊㘄 2.5 䛾䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝ᝈ⪅䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯ᕷ ㈍ᚋㄪᰝ䛻䛚䛔䛶䚸65 ṓ௨ୖཬ䜃 65 ṓᮍ‶䛷ẚ㍑䛧䛯䛸䛣䜝䚸65 ṓ௨ୖ䛾䛷స⏝Ⓨ⌧ ⋡䛜㧗䛔ഴྥ䛜ㄆ䜑䜙䜜䛯䚹䜎䛯䚸75 ṓ௨ୖཬ䜃 75 ṓᮍ‶䛷ẚ㍑䛧䛯䛸䛣䜝䚸75 ṓ௨ୖ䛾 䛷䛿㣗ḧ䚸ᗁぬ䚸㉳❧ᛶప⾑ᅽ䚸ᝏᚰ䚸Ṍ⾜ᅔ㞴䛾Ⓨ⌧⋡䛜㧗䛔ഴྥ䛜ㄆ䜑䜙 䜜䛯䚹䛣䜜䜙䛾⤖ᯝ䜢䛖䛡䚸ᮏ㡯┠䜢タᐃ䛧䛯䚹 10䠊 ዷ፬䚸⏘፬䚸ᤵங፬➼䜈䛾ᢞ ዷ፬䚸⏘፬䚸ᤵங፬➼䜈䛾ᢞ (1) ዷፎ୰䛾ᢞ䛻㛵䛩䜛Ᏻᛶ䛿☜❧䛧䛶䛔䛺䛔䛾䛷䚸ዷ፬ཪ䛿ዷፎ䛧䛶䛔䜛ྍ⬟ᛶ䛾䛒䜛፬ே 䛻䛿䚸⒪ୖ䛾᭷┈ᛶ䛜༴㝤ᛶ䜢ୖᅇ䜛䛸ุ᩿䛥䜜䜛ሙྜ䛻䛾䜏ᢞ䛩䜛䛣䛸䚹 (2) ື≀ᐇ㦂䛷䚸ஙỒ୰䜈䛾⛣⾜䛜ሗ࿌䛥䜜䛶䛔䜛䛾䛷䚸ᮏᢞ୰䛿ᤵங䜢㑊䛡䛥䛫䜛䛣䛸䚹 (1) ⸆Ⓨ➨ 607 ྕ䠄ᖹᡂ 9 ᖺ 4 ᭶ 25 ᪥䠅䛻䜘䜛䚹 (2) ື≀ᐇ㦂䛷ஙỒ⛣⾜䚸⫾┙㏻㐣䛜ሗ࿌䛥䜜䛶䛔䜛䛾䛷ᮏ㡯┠䜢タᐃ䛧䛯 52,53)䚹 45 11䠊 ᑠඣ➼䜈䛾ᢞ ᑠඣ➼䜈䛾ᢞ ᑠඣ䛻ᑐ䛩䜛Ᏻᛶ䛿☜❧䛧䛶䛔䛺䛔䠄⏝⤒㦂䛜䛺䛔䠅䚹 ⸆Ⓨ➨ 607 ྕ䠄ᖹᡂ 9 ᖺ 4 ᭶ 25 ᪥䠅䛻䜘䜛䚹 12䠊 ⮫ᗋ᳨ᰝ⤖ᯝ䛻ཬ䜌䛩ᙳ㡪 ヱᙜ䛧䛺䛔䚹 13䠊 㐣㔞ᢞ 㐣㔞ᢞ ᮏ䛾㐣㔞ᢞ䛻䜘䜚 MAO-B 䛾㑅ᢥⓗ㜼ᐖస⏝䛜పୗ䛧䚸㠀㑅ᢥⓗ MAO 㜼ᐖ䛻䜘䜛స⏝䛜Ⓨ ⌧䛩䜛䛣䛸䛜䛒䜛䛸⪃䛘䜙䜜䜛䛾䛷䚸ḟ䛾ᝈ⪅䛾≧ែ䛻䛿༑ศὀព䛩䜛䛣䛸䚹 (1) 㐣㔞ᢞ䛻䜘䜛䛸ᛮ䜟䜜䜛ୗグ䛾≧䛜䛒䜙䜟䜜䛯ᝈ⪅䠷㑅ᢥᛶ䛜పୗ䛧䛯ሙྜ䚸䝗䝟䝭䞁ཬ䜃䝜 䝹䜶䝢䝛䝣䝸䞁䛾స⏝䜢ቑᙉ䛩䜛䛚䛭䜜䛜䛒䜛䚹䠹 1) ⢭⚄⚄⤒⣔ ኻ⚄䚸⃭㉺䚸╀Ẽ䚸ᗁぬ䚸ዶ䚸②ᨥ䚸⮬ẅⓗ⾜ື䚸⑵࿈䚸Ᏻ䚸╀䚸ᢚ䛖䛴䚸 ⚄⤒㐣ᩄ䚸㢌③䚸↓ື䜔ᡓ䛾ᝏ➼ 2)ᚠ⎔ჾ 䝅䝵䝑䜽䚸⾑ᅽୖ᪼䚸㉳❧ᛶప⾑ᅽ䚸ᚰஹ㐍䚸⣚₻䚸ᩚ⬦䚸⾑ᅽపୗ䚸Ⓨờ➼ 3)䛭䛾 ㉸㧗⇕䚸྾ᢚไ䛸䚸ୗ⬚㒊③䚸㛤ཱྀ㞀ᐖ➼ (2) 㧗⾑ᅽ䛾䛒䜛ᝈ⪅䠷㠀㑅ᢥⓗ MAO 㜼ᐖ䛷⚗ᚷ䛸䛺䛳䛶䛚䜚䚸㑅ᢥᛶ䛜పୗ䛧䛯ሙྜ䜢⪃៖䛧 䛶グ㍕䛧䛯䚹䠹 (3) 〓Ⰽ⣽⬊⭘䛾䛒䜛ᝈ⪅䠷㠀㑅ᢥⓗ MAO 㜼ᐖ䛷⚗ᚷ䛸䛺䛳䛶䛚䜚䚸㑅ᢥᛶ䛜పୗ䛧䛯ሙྜ䜢⪃ ៖䛧䛶グ㍕䛧䛯䚹䠹 (4) ⥳ෆ㞀䛾䛒䜛ᝈ⪅䠷㠀㑅ᢥⓗ MAO 㜼ᐖ䛷ៅ㔜ᢞ䛸䛺䛳䛶䛚䜚䚸㑅ᢥᛶ䛜పୗ䛧䛯ሙྜ䜢⪃ ៖䛧䛶グ㍕䛧䛯䚹䠹 (5) ⢾ᒀ䛾䛒䜛ᝈ⪅䠷㠀㑅ᢥⓗ MAO 㜼ᐖ䛷ៅ㔜ᢞ䛸䛺䛳䛶䛚䜚䚸㑅ᢥᛶ䛜పୗ䛧䛯ሙྜ䜢⪃ ៖䛧䛶グ㍕䛧䛯䚹䠹 ฎ⨨䠖྾䜢ಖㆤ䛩䜛䛯䜑Ẽ㐨䜢☜ಖ䛧䚸ᚲせ䛺䜙䜀⿵㊊ⓗ䛺㓟⣲䛾⏝ཬ䜃ேཱྀ྾ჾ䛾⏝䜢 ྵ䜑㐺ษ䛻⟶⌮䛩䜛䚹᭹⏝ᚋ▷㛫䛷䛒䜜䜀ദྤ䚸άᛶⅣᢞ䚸⫶Ὑί䜢⾜䛖䚹୰ᯡ⚄⤒⣔䛾่⃭ 䠄②ᨥ䜢ྵ䜐䠅䛾ᚩೃ䛸≧䛿䝆䜰䝊䝟䝮䛾Ⅼ㟼ὀ䛷⒪䛩䜛䚹㐣ᗘ䛾ప⾑ᅽ䜔䝗䝟䝭䞁ཬ䜃䝜䝹䜶 䝢䝛䝣䝸䞁㐣䛻䜘䜛≧䛾ᝏ䛜䜏䜙䜜䛯ሙྜ䛻䛿⿵ᾮ䛾Ⅼ㟼ὀ➼䛾ᑐ⒪ἲ䜢⾜䛖䛣䛸䚹䝅䝵䝑 䜽䛻䛿䝠䝗䝻䝁䝹䝏䝌䞁䜢㟼ὀ㐺⏝䛩䜛䚹⥴Ᏻ䚸⃭㉺䚸ᶵᲔⓗ䛺෭༷䛻ᛂ䛧䛺䛔㧗య 䛻 䛿䚸䜽䝻䝹䝥䝻䝬䝆䞁ሷ㓟ሷ䜢㐺⏝䛩䜛䚹㐣ᗘ䛾⾑ᅽୖ᪼䛜䛒䜙䜟䜜䛯ሙྜ䛻䛿䃐-㐽᩿䠄䝣䜵䞁䝖䝷 䝭䞁➼䠅䛾Ⅼ㟼ὀ➼䛾ᑐ⒪ἲ䜢⾜䛖䛣䛸䚹 46 14䠊 㐺⏝ୖ䛾ὀព 㐺⏝ୖ䛾ὀព (1) ⸆ PTP ໟ䛾⸆䛿 PTP 䝅䞊䝖䛛䜙ྲྀ䜚ฟ䛧䛶᭹⏝䛩䜛䜘䛖ᣦᑟ䛩䜛䛣䛸䚹䠷PTP 䝅䞊䝖䛾ㄗ㣧䛻䜘 䜚䚸◳䛔㗦ゅ㒊䛜㣗㐨⢓⭷䜈่ධ䛧䚸᭦䛻䛿✸Ꮝ䜢㉳䛣䛧䛶⦪㝸Ὕ⅖➼䛾㔜⠜䛺ྜే䜢ేⓎ 䛩䜛䛣䛸䛜ሗ࿌䛥䜜䛶䛔䜛䚹䠹 (2) ᭹⏝ 1) ᮏ䛿⯉䛾ୖ䛻䛾䛫ၚᾮ䜢ᾐ₶䛥䛫⯉䛷㍍䛟䛴䜆䛧䚸ᔂቯᚋၚᾮ䛾䜏䛷᭹⏝ྍ⬟䛷䛒䜛䚹䜎 䛯䚸Ỉ䛷᭹⏝䛩䜛䛣䛸䜒䛷䛝䜛䚹 2) ᮏ䛿ᐷ䛯䜎䜎䛾≧ែ䛷䛿䚸Ỉ䛺䛧䛷᭹⏝䛥䛫䛺䛔䛣䛸䚹 15䠊 䛭䛾䛾ὀព 䛭䛾䛾ὀព (1) 䜶䝣䝢䞊㘄 2.5 䛾䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯ᅜෆ䛾 ⮫ᗋヨ㦂䛻䛶䚸᫂䜙䛛䛻ᅉᯝ㛵ಀ䛜ྰᐃฟ᮶䛺䛔ᢚ䛖䛴䛛䜙䛾⮬ẅ䛜 488 ୰ 2 䛻ㄆ䜑䜙 䜜䛯䚹 (2) 㐣㔞㐃⏝䛻䜘䜚䚸౫ᏑᛶⓎ⌧䛾ྍ⬟ᛶ䛜䛒䜛䚹 (1) 䜶䝣䝢䞊㘄 2.5 䛾䝺䝪䝗䝟ྵ᭷〇ే⏝ཬ䜃㠀ే⏝䛾䝟䞊䜻䞁䝋䞁ᝈ⪅䜢ᑐ㇟䛸䛧䛯➨䊢┦ ヨ㦂 10)䛷⮬ẅ 2 䛜ሗ࿌䛥䜜䛯䛯䜑䚹 (2) 㐣㔞㐃⏝䛻䛶䚸௦ㅰ≀䛷䜒䛒䜛 "-䝯䝍䞁䝣䜵䝍䝭䞁䜔 "-䜰䞁䝣䜵䝍䝭䞁䛾⾑୰⃰ᗘ䛜㧗䜎䜛ᜍ䜜䛜 䛒䜚䚸౫ᏑᛶⓎ⌧䛾ྍ⬟ᛶ䛜ྰᐃ䛷䛝䛺䛔䛯䜑䚹 16䠊 䛭䛾 ヱᙜ䛧䛺䛔䚹 47 䊨䠊㠀⮫ᗋヨ㦂䛻㛵䛩䜛㡯┠ 䠍䠊 ⸆⌮ヨ㦂 (1) ⸆ຠ⸆⌮ヨ㦂䠄䛂䊥䠊⸆ຠ⸆⌮䛻㛵䛩䜛㡯┠䛃ཧ↷䠅 (2) ḟⓗ⸆⌮ヨ㦂 ヱᙜ㈨ᩱ䛺䛧䚹 (3) Ᏻᛶ⸆⌮ヨ㦂 1) ୰ᯡ⚄⤒⣔䛻ᑐ䛩䜛స⏝ 73) 䝬䜴䝇䛻ᑐ䛧䛶䚸0.08䚸0.8 ཬ䜃 8mg/kg 䛾⤒ཱྀᢞ䜢⾜䛳䛯䛜䚸䛔䛪䜜䛾⏝㔞䛻䛚䛔䛶䜒䝏 䜸䝨䞁䝍䞊䝹╧╀䛾ቑᙉ䛻ᑐ䛩䜛ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹 2) ྾䞉ᚠ⎔ჾ⣔䛻ᑐ䛩䜛స⏝ 73) 0.8mg/kg 㟼ὀ䠄䝡䞊䜾䝹≟䠅௨ୖ䛷୍㐣ᛶ䠄⣙ 2 ศ㛫䠅䛾⾑ᅽపୗ䚸ᚰᢿᩘ䛾㍍ᗘ䛾ቑຍ䚸 ⭣ື⬦⾑ὶ䛾୍㐣ᛶ䛾ቑຍ䛜ㄆ䜑䜙䜜䛯䠄⮫ᗋ⏝㔞䛾 10 ಸ௨ୖ䠅䚹ฟᚰᡣ䠄䝰䝹䝰䝑 䝖䠅䛻ᑐ䛧䚸10䃛g/mL 䛷⦰ຊ䛾పୗ䛜ㄆ䜑䜙䜜䛯䠄⮫ᗋ⏝㔞䛾 10 ಸ௨ୖ䠅䚹 3) ฟ⮚ჾ䛻ᑐ䛩䜛స⏝ 73) ฟᅇ⭠䠄䜴䝃䜼䠅ཬ䜃ฟᏊᐑ䠄䝷䝑䝖䠅䛾⮬ື㐠ື䛾ᢚไ䛜ㄆ䜑䜙䜜䛯䚹 4) ⮬ᚊ⚄⤒సື⸆䛻ᑐ䛩䜛స⏝ 73) 䜰䝉䝏䝹䝁䝸䞁䚸ሷ䝞䝸䜴䝮ཬ䜃䝠䝇䝍䝭䞁䛻ᑐ䛧䚸䝰䝹䝰䝑䝖䛾ฟᅇ⭠⦰స⏝䛾ᢚไ䛜 ㄆ䜑䜙䜜䛯䚹䝤䝷䝆䜻䝙䞁䛾⦰స⏝䛻ᑐ䛩䜛ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹 5) ᾘ⟶䛻ᑐ䛩䜛స⏝ 73) 䝬䜴䝇䛻ᑐ䛧䛶䚸0.08䚸0.8 ཬ䜃 8mg/kg 䛾⤒ཱྀᢞ䜢⾜䛳䛯䛜䚸䛔䛪䜜䛾㔞䛻䛚䛔䛶䜒ᾘ ⟶㍺㏦⬟䛻ᑐ䛩䜛ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹 䝷䝑䝖䛾ᗃ㛛⤖⣻₽⒆䛻ᑐ䛧䚸0.008䚸0.08 ཬ䜃 0.8mg/kg 䛾⤒ཱྀᢞ䜢⾜䛳䛯䛜䚸䛔䛪䜜䛾 ⏝㔞䛻䛚䛔䛶䜒ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹 6) ⾑ᾮ䛻ᑐ䛩䜛స⏝ 73) ⁐⾑స⏝䚸⾑ᑠᯈจ㞟⬟䛻ᑐ䛩䜛ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䠄䝠䝖⾑ᾮ䠅䚹 7) ⭈ᶵ⬟䛻ཬ䜌䛩ᙳ㡪 73) 䝷䝑䝖䛻ᑐ䛧䛶䚸0.008䚸0.08 ཬ䜃 0.8mg/kg 䛾⤒ཱྀᢞ䜢⾜䛳䛯䛜䚸䛔䛪䜜䛾⏝㔞䛻䛚䛔䛶 䜒⭈ᶵ⬟䛻ᑐ䛩䜛ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹 48 8) ᢠ⅖స⏝ 73) 䝬䜴䝇䛾 0.6䠂㓑㓟⭡⭍ෆᢞ䛻䜘䜛⾑⟶㏱㐣ᛶஹ㐍䛻ᑐ䛧䚸0.008䚸0.08 ཬ䜃 0.8mg/kg 䛾⤒ཱྀᢞ䜢⾜䛳䛯䛜䚸䛔䛪䜜䛾⏝㔞䛻䛚䛔䛶䜒ᙳ㡪䛿ㄆ䜑䜙䜜䛺䛛䛳䛯䚹 9) ⬻Ἴ䛻ཬ䜌䛩ᙳ㡪 74) 䝷䝑 䝖䛻䝉 䝺䜼䝸䞁ሷ㓟ሷ䠄 1.5mg/kg䠅 䚸"-䜰䞁䝣䜵 䝍䝭 䞁䠄 10mg/kg䠅 䚸 d-䜰䞁䝣䜵 䝍䝭䞁 䠄1mg/kg䠅䚸d"-䜰䞁䝣䜵䝍䝭䞁䠄5mg/kg䠅䚸䝉䝺䜼䝸䞁ሷ㓟ሷ䛾 d-య␗ᛶయ䠄1.5mg/kg䠅䜢⤒ཱྀ ᢞ䛧䛯ᚋ䚸⬻Ἴ࿘Ἴᩘ䛾ኚ䜢ẚ㍑䛧䛯䚹䝉䝺䜼䝸䞁ሷ㓟ሷ䛸"-䜰䞁䝣䜵䝍䝭䞁䛻䜘䛳䛶ច㉳ 䛥䜜䛯ⴭ᫂䛺࿘Ἴᩘ䛾⛣ື䛿 d-䜰䞁䝣䜵䝍䝭䞁䚸d"-䜰䞁䝣䜵䝍䝭䞁ཬ䜃䝉䝺䜼䝸䞁ሷ㓟ሷ䛾 dయ␗ᛶయ䛷ច㉳䛥䜜䛯 EEG 䛾ኚ䛸䛿᫂☜䛻༊ู䛩䜛䛣䛸䛜䛷䛝䛯䚹 (4) 䛭䛾䛾⸆⌮ヨ㦂 ヱᙜ㈨ᩱ䛺䛧䚹 䠎䠊 ẘᛶヨ㦂 (1) ༢ᅇᢞẘᛶヨ㦂 74,75) ື≀✀ LD50䠄mg/kg䠅 ᢞ⤒㊰ 䝬䜴䝇 䝷䝑䝖 䜲䝚 ⤒ཱྀ ⓶ୗ 㟼ὀ ⤒ཱྀ ⓶ୗ 㟼ὀ ⤒ཱྀ 㞝 㞤 445.3 206.0 49.8 422.0 146.1 75.4 200.0 365.3 190.0 50.6 302.6 112.3 69.8 200.0 (2) ᢞẘᛶヨ㦂 1) 䝷䝑䝖 14 ᪥㛫⤒ཱྀᢞ 䝷䝑䝖䠄㞤㞝䠅䛻ᑐ䛧䛶䚸80mg/kg/᪥䜢 14 ᪥㛫ᙉไ⤒ཱྀᢞ䛧䛯䛸䛣䜝䚸㞤㞝䛸䜒 20 ༉୰ 12 ༉䛜Ṛஸ䛧䛯 77)䚹 2) 䝷䝑䝖 13 㐌㛫⤒ཱྀᢞ 䝷䝑䝖䠄㞤㞝䠅䛻ᑐ䛧䛶 10䚸25䚸60 ཬ䜃 90mg/kg/᪥䜢 13 㐌㛫ΰ㣵⤒ཱྀᢞ䛧䛯䛸䛣䜝䚸᭱ప ⏝㔞䛾 10mg/kg/᪥䛷䜒య㔜ቑຍ䛾ᢚไ䛜ㄆ䜑䜙䜜䚸↓ẘᛶ㔞䛿 10mg/kg/᪥ᮍ‶䛸⪃䛘䜙 䜜䛯 78)䚹 3) 䝷䝑䝖 52 㐌㛫⤒ཱྀᢞ 䝷䝑䝖䠄㞤㞝䠅䛻 0.7䚸3.5 ཬ䜃 17.5mg/kg/᪥䜢 52 㐌㛫ΰ㣵⤒ཱྀᢞ䛧䛯⤖ᯝ䚸⏝㔞౫Ꮡⓗ䛺 య㔜ቑຍᢚไ䛜䜏䜙䜜䛯䛜䚸⮫ᗋ᳨ᰝ್ཬ䜃⌮⤌⧊ⓗᡤぢ䛷䛿␗ᖖ䛿ㄆ䜑䜙䜜䛺䛛䛳䛯 79) 䚹 49 4) 䝡䞊䜾䝹≟ 52 㐌㛫⤒ཱྀᢞ 䝡䞊䜾䝹≟䠄㞤㞝䠅䛻 1䚸4 ཬ䜃 16mg/kg/᪥䜢 52 㐌㛫⤒ཱྀᢞ䛧䛯⤖ᯝ䚸4䚸16mg/kg/᪥ᢞ 䛷⸆⌮άᛶ䛻䜘䜛䜒䛾䛸⪃䛘䜙䜜䜛άືᛶ䛾ஹ㐍䚸ὸ㏿྾䚸㐠ື䚸ᢚไཪ䛿ไṆ⾜ ື䚸ⓑṑ⫗䚸ၚᾮศἪ㐣ከ➼䛾ᚩೃཬ䜃య㔜ቑຍ䛾ᢚไ䛜䜏䜙䜜䛯䚹⮫ᗋ᳨ᰝ್䛷䛿 GPT䚸Al-P䚸䝁䝺䝇䝔䝻䞊䝹ཬ䜃୰ᛶ⬡⫫䛾ቑຍ䛜䜏䜙䜜䛯䚹⾑ᾮᏛⓗ᳨ᰝ䛷䛿㉥⾑⌫ᐜ ✚䚸䝦䝰䜾䝻䝡䞁ཬ䜃㉥⾑⌫ᩘ䛾ῶᑡ䛜䜏䜙䜜䛯䚹๗᳨ᡤぢ䛷䛿 16mg/kg/᪥ᢞ䛷ᬯⰍ ⫢䛸⫢㔜㔞䛾ቑຍཬ䜃⭁⮚㔜㔞䛾ῶᑡ䛜䜏䜙䜜䛯䚹4mg/kg/᪥ᢞ䛷䛿⭁⮚㔜㔞䛾ῶᑡ 䛜䜏䜙䜜䛯䚹⌮Ꮫⓗᡤぢ䛷䛿 16mg/kg/᪥ᢞ䛷⭁⮚䛾ⴎ⦰ཬ䜃⬚⭢䛾㏥⦰䛜䜏䜙䜜䛯 80)䚹 (3) ⏕ṪⓎ⏕ẘᛶヨ㦂 䝷䝑䝖ዷፎ๓䚸ዷፎᮇ䚸ᤵஙᮇ⤒ཱྀᢞ䠄1䚸4䚸16mg/kg/᪥䠅䚸䝷䝑䝖ჾᐁᙧᡂᮇ⤒ཱྀᢞ䠄4䚸12䚸 36mg/kg/᪥䠅䚸䜴䝃䜼ჾᐁᙧᡂᮇ⤒ཱྀᢞ䠄5䚸25䚸50mg/kg/᪥䠅䚸䝷䝑䝖࿘⏘ᮇ䚸ᤵஙᮇ⤒ཱྀᢞ 䠄4䚸16䚸64mg/kg/᪥䠅䛻䛶䛔䛪䜜䛾ヨ㦂䛻䛚䛔䛶䜒⫾ẘᛶ䞉ദወᙧᛶస⏝䛿ㄆ䜑䜙䜜䛺䛛 䛳䛯 81䡚84)䚹 (4) 䛭䛾䛾≉Ṧẘᛶ 1) ౫Ꮡᛶ 䝷䝑䝖䛻 4䚸5mg/kg/᪥䜢⤒ཱྀᢞ䛧䛯⤖ᯝ䚸㌟య౫Ꮡᛶ䛿ㄆ䜑䜙䜜䛺䛛䛳䛯 85,86)䚹 䜎䛯䚸䝷䝑䝖䛾䜰䞁䝣䜵䝍䝭䞁ᵝᘚู่⃭ヨ㦂䛷䛿䚸㧗⏝㔞䠄17䚸30mg/kg/᪥䠅䛷䜰䞁䝣䜵䝍䝭䞁 䛸ỗ䛧䛯 87)䚹 2) ᢠཎᛶ ⬟ືⓗ㌟ᛶ䜰䝘䝣䜱䝷䜻䝅䞊䠄ASA䠅ᛂ䠄䝰䝹䝰䝑䝖䠅ཬ䜃 IgE ᢠయ⏘⏕⬟䜢ᣦᶆ䛸䛧䛯䝷 䝑䝖ᢠ PCA ᛂ䠄ឤస䝬䜴䝇䠅୪䜃䛻㛫᥋㉥⾑⌫จ㞟䠄PHA䠅ᛂ䠄ឤస䝬䜴䝇䠅䛻䜘䛳䛶᳨ ウ䛧䛯䛜䚸䛔䛪䜜䜒㝜ᛶ䛷䛒䛳䛯 88)䚹 3) 㑇ఏẘᛶ 㑇ఏᏊ✺↛ኚ␗䠄AMES ヨ㦂䠅䚸ᰁⰍయ䜈䛾ᙳ㡪䛊ᑠ᰾ヨ㦂䠄䝷䝑䝖䚸䝬䜴䝇䠅䚸㦵㧊⣽⬊䛷䛾 ᰁⰍయ␗ᖖヨ㦂䠄䝷䝑䝖䠅䛋䛻ᑐ䛩䜛ᙳ㡪䜢᳨ウ䛧䛯䛜䚸䛔䛪䜜䜒㝜ᛶ䛷ኚ␗ཎᛶ䛿ㄆ䜑䜙䜜 䛺䛛䛳䛯 89䡚92)䚹 4) 䛜䜣ཎᛶ 䝷䝑䝖䚸䝬䜴䝇䜢⏝䛔䛶ヨ㦂䛧䛯䛸䛣䜝䚸䛔䛪䜜䛻䛚䛔䛶䜒䛜䜣ཎᛶ䛿ㄆ䜑䜙䜜䛺䛛䛳䛯 93,94)䚹 50 䊩䠊⟶⌮ⓗ㡯䛻㛵䛩䜛㡯┠ 䠍䠊 つไ༊ศ 〇䠖䜶䝣䝢䞊OD 㘄 2.5 ⸆䚸ぬ䛫䛔ཎᩱ䚸ฎ᪉⟢་⸆ရ䠄ὀព䠉་ᖌ➼䛾ฎ᪉⟢䛻䜘䜚⏝䛩䜛䛣䛸䠅 ᭷ຠᡂศ䠖䝉䝺䜼䝸䞁ሷ㓟ሷ ⸆䚸ぬ䛫䛔ཎᩱ 䠎䠊 ᭷ຠᮇ㛫ཪ䛿⏝ᮇ㝈 ⏝ᮇ㝈䠖3 ᖺ 䠏䠊 ㈓ἲ䞉ಖᏑ᮲௳ ᐊ ಖᏑ䚸Ẽᐦᐜჾ䚹 㛤ᑒᚋ䚸┤ᑕ᪥ගཬ䜃㧗 䞉㧗‵䜢㑊䛡䛶ಖᏑ䛩䜛䛣䛸䚹 䠐䠊 ⸆ྲྀᢅ䛔ୖ䛾ὀពⅬ (1) ⸆ᒁ䛷䛾ྲྀ䜚ᢅ䛔ୖ䛾␃ពⅬ䛻䛴䛔䛶 1) ᡂศ䛷䛒䜛䝉䝺䜼䝸䞁ሷ㓟ሷ䛿ぬ䛫䛔ཎᩱ䛻ᣦᐃ䛥䜜䛶䛔䜛䛯䜑䚸ぬ䛫䛔ྲྀ⥾ἲ䛻 ๎䛳䛶ྲྀ䜚ᢅ䛖䚹 2) ᗫᲠ䛧䜘䛖䛸䛩䜛㝿䛻䛿䚸㝔➼䛾㛤タ⪅䛜㒔㐨ᗓ┴䛻ᒆ䛡ฟ䛶䚸㒔㐨ᗓ┴⫋ဨ䛾❧䛔 䛾ୗ䛻ᗫᲠ䛩䜛䚹ධ㝔ᝈ⪅䛾Ṛஸ䜔ฎ᪉ኚ᭦䠄ᢞ⸆୰Ṇ䜔ῶ㔞䠅➼䛻䜘䜚ṧ䛳䛯ぬ䛫䛔 ཎᩱ䜒䚸㝔➼䛾㛤タ⪅䛜㒔㐨ᗓ┴䛻ᒆ䛡ฟ䛶䚸㒔㐨ᗓ┴⫋ဨ䛾❧䛔䛾ୗ䛻ᗫᲠ䛩䜛䚹 3) ᝈ⪅䠄䛭䛾ᐙ᪘䜢ྵ䜐䠅䛜せ䛸䛺䛳䛯ぬ䛫䛔ཎᩱ䜢㝔➼ཪ䛿⸆ᒁ䜈ᣢཧ䛧䛶䜒ㆡ䜚ཷ 䛡䜛䛣䛸䛿䛷䛝䛺䛔䛾䛷䚸ᝈ⪅䠄䛭䛾ᐙ᪘䜢ྵ䜐䠅⮬㌟䛷ᗫᲠ䛩䜛䜘䛖ᣦᑟ䛩䜛䚹ᝈ⪅䠄䛭䛾ᐙ ᪘䜢ྵ䜐䠅䛜⾜䛖ᗫᲠ䜢⿵ຓ䛩䜛䛣䛸䛿ᕪ䛧ᨭ䛘䛺䛔䚹 4) 䛭䛾䚸ヲ⣽䛻䛴䛔䛶䛿䚸ྲྀ䜚ᢅ䛔䛾ᡭᘬ䛝䛸䛧䛶ᖹᡂ 12 ᖺ 9 ᭶䛻ཌ⏕┬་⸆Ᏻᒁ㯞⸆ ㄢ䜘䜚䛂㝔䞉デ⒪ᡤ䞉㣫⫱ື≀デ⒪タ䞉⸆ᒁ䛻䛚䛡䜛ぬ䛫䛔ཎᩱྲྀᢅ䛔䛾ᡭᘬ䛝䛃䛜ฟ 䛥䜜䛶䛔䜛䛾䛷ཧ↷䛾䛣䛸䚹᫂Ⅼ䛻䛴䛔䛶䛿ಖᡤ䜎䛯䛿㒔㐨ᗓ┴ᗇ⸆ົㄢ䛻ၥ䛔ྜ䜟 䛫䜛䚹 (2) ⸆䛾ྲྀ䜚ᢅ䛔䛻䛴䛔䛶䠄ᝈ⪅➼䛻␃ព䛩䜉䛝ᚲ㡲㡯➼䠅 1) PTP ໟ䛾⸆䛿 PTP 䝅䞊䝖䛛䜙ྲྀ䜚ฟ䛧䛶᭹⏝䛩䜛䜘䛖ᣦᑟ䛩䜛䛣䛸䚹 ᮏ䛿⯉䛾ୖ䛻䛾䛫ၚᾮ䜢ᾐ₶䛥䛫⯉䛷㍍䛟䛴䜆䛧䚸ᔂቯᚋၚᾮ䛾䜏䛷᭹⏝ྍ⬟䛷䛒䜛䚹 䜎䛯䚸Ỉ䛷᭹⏝䛩䜛䛣䛸䜒䛷䛝䜛䚹䛯䛰䛧䚸ᮏ䛿ᐷ䛯䜎䜎䛾≧ែ䛷䛿䚸Ỉ䛺䛧䛷᭹⏝䛥䛫䛺䛔 䛣䛸䚹䠄䛂䊧䠊Ᏻᛶ䠄⏝ୖ䛾ὀព➼䠅䛻㛵䛩䜛㡯┠ 14䠊㐺ᛂୖ䛾ὀព䛃䜢ཧ↷䠅 2) ぬ䛫䛔ྲྀ⥾ἲ䛻䜘䜚䚸ᮏ䛾䜢ཷ䛡䛯ᝈ⪅䠄䜎䛯䛿䛭䛾┳ㆤ䛻ᙜ䛯䜛⪅䠅䛿䚸➨୕⪅ 䛻ᮏ䜢ㆡ䜚Ώ䛩䛣䛸䜢⚗䛨䜙䜜䛶䛔䜛䚹 (3) ㄪ䛾␃ពⅬ䛻䛴䛔䛶 ヱᙜ䛧䛺䛔䚹 51 䠑䠊 ᢎㄆ᮲௳➼ ヱᙜ䛧䛺䛔䚹 䠒䠊 ໟ PTP 30 㘄 䠄10 㘄㽢3䠅 PTP100 㘄 䠄10 㘄㽢10䠅 䠓䠊 ᐜჾ䛾ᮦ㉁ PTP ໟ䠖䝫䝸ሷ䝡䝙䝹䞉䝫䝸ሷ䝡䝙䝸䝕䞁䝷䝭䝛䞊䝖䝣䜱䝹䝮䚸䜰䝹䝭䝙䜴䝮⟩ 䜰䝹䝭䝙䜴䝮⿄䠖䜰䝹䝭䝙䜴䝮䞉䝫䝸䜶䝏䝺䞁䝷䝭䝛䞊䝖䝣䜱䝹䝮 䠔䠊 ྠ୍ᡂศ䞉ྠຠ⸆ ྠ୍ᡂศ⸆䠖䜶䝣䝢䞊㘄 2.5 ྠຠ⸆䠖䝺䝪䝗䝟䚸䝺䝪䝗䝟䞉䝧䞁䝉䝷䝆䝗ሷ㓟ሷ䚸䝺䝪䝗䝟䞉䜹䝹䝡䝗䝟Ỉ≀䚸 䝤䝻䝰䜽䝸䝥䝏䞁䝯䝅䝹㓟ሷ䚸䝨䝹䝂䝸䝗䝯䝅䝹㓟ሷ䚸䝍䝸䝨䜻䝋䞊䝹ሷ㓟ሷ䚸 䜹䝧䝹䝂䝸䞁䚸䝥䝷䝭䝨䜻䝋䞊䝹ሷ㓟ሷỈ≀䚸䝖䝸䝦䜻䝅䝣䜵䝙䝆䝹ሷ㓟ሷ䚸 䝗䝻䜻䝅䝗䝟䚸䜰䝬䞁䝍䝆䞁ሷ㓟ሷ䚸䝻䝢䝙䝻䞊䝹ሷ㓟ሷ䚸䜶䞁䝍䜹䝫䞁➼ 䠕䠊 ᅜ㝿ㄌ⏕ᖺ᭶᪥ 1980 ᖺ 3 ᭶ 14 ᪥ 10䠊 〇㐀㈍ᢎㄆᖺ᭶᪥ཬ䜃ᢎㄆ␒ྕ 〇㐀㈍ᢎㄆᖺ᭶᪥䠖2007 ᖺ 3 ᭶ 15 ᪥ ᢎㄆ␒ྕ䠖21900AMX00554000 11䠊 ⸆౯ᇶ‽㍕ᖺ᭶᪥ 2007 ᖺ 7 ᭶ 6 ᪥ 12䠊 ຠ⬟ཪ䛿ຠᯝ㏣ຍ䚸⏝ἲཬ䜃⏝㔞ኚ᭦㏣ຍ➼䛾ᖺ᭶᪥ཬ䜃䛭䛾ෆᐜ 2015 ᖺ 12 ᭶ 21 ᪥䠖䛂ຠ⬟䞉ຠᯝ䛃ཬ䜃䛂⏝ἲ䞉⏝㔞䛃䛾㏣ຍ ຠ⬟䞉ຠᯝ䠖䝟䞊䜻䞁䝋䞁䠄䝺䝪䝗䝟ྵ᭷〇䜢ే⏝䛧䛺䛔ሙྜ䠖Yahr 㔜ᗘ䝇䝔䞊䝆䊠䡚䊢䠅 ⏝ἲ䞉⏝㔞䠖䝺䝪䝗䝟ྵ᭷〇䜢ే⏝䛧䛺䛔ሙྜ ㏻ᖖ䚸ᡂே䛻䝉䝺䜼䝸䞁ሷ㓟ሷ䛸䛧䛶 1 ᪥ 1 ᅇ 2.5mg 䜢ᮅ㣗ᚋ᭹⏝䛛䜙ጞ䜑䚸2 㐌 䛤䛸䛻 1 ᪥㔞䛸䛧䛶 2.5mg 䛪䛴ቑ㔞䛧䚸1 ᪥ 10mg 䛸䛩䜛䚹1 ᪥㔞䛜䝉䝺䜼䝸䞁ሷ㓟 ሷ䛸䛧䛶 5.0mg ௨ୖ䛾ሙྜ䛿ᮅ㣗ཬ䜃㣗ᚋ䛻ศ᭹䛩䜛䚹䛯䛰䛧䚸7.5mg 䛾ሙྜ䛿 ᮅ㣗ᚋ 5.0mg ཬ䜃㣗ᚋ 2.5mg 䜢᭹⏝䛩䜛䚹 䛺䛚䚸ᖺ㱋䚸≧䛻ᛂ䛨䛶㐺ᐅቑῶ䛩䜛䛜 1 ᪥ 10mg 䜢㉸䛘䛺䛔䛣䛸䛸䛩䜛䚹 52 13䠊 ᑂᰝ⤖ᯝ䚸ホ౯⤖ᯝබ⾲ᖺ᭶᪥ཬ䜃䛭䛾ෆᐜ 䠘ཧ⪃䠖䜶䝣䝢䞊㘄 2.5䠚 ᑂᰝ⤖ᯝ䠖 ⸆ἲ➨ 14 ᮲➨ 2 㡯➨ 3 ྕ䜲䛛䜙䝝䜎䛷䠄ᢎㄆᣄྰ⏤䠅䛾䛔䛪䜜䛻䜒ヱᙜ䛧䛺䛔䚹 ᑂᰝ⤖ᯝ㏻▱᪥䠖 2009 ᖺ 12 ᭶ 21 ᪥ 14䠊 ᑂᰝᮇ㛫 䠘ཧ⪃䠖䜶䝣䝢䞊㘄 2.5䠚 6 ᖺ㛫䠄1998 ᖺ 7 ᭶ 3 ᪥䡚2004 ᖺ 7 ᭶ 2 ᪥䠄⤊䠅䠅 15䠊 ᢞ⸆ᮇ㛫ไ㝈་⸆ရ䛻㛵䛩䜛ሗ ᮏ䛿䚸ᢞ⸆ᮇ㛫䛻㛵䛩䜛ไ㝈䛿ᐃ䜑䜙䜜䛶䛔䛺䛔䚹 16䠊 ྛ✀䝁䞊䝗 䜶䝣䝢䞊OD 㘄 2.5 ໟつ᱁ ཌ⏕ປാ┬ ⸆౯ᇶ‽㍕ ་⸆ရ䝁䞊䝗 䝺䝉䝥䝖 㟁⟬䝁䞊䝗 1169010F2020 620005364 HOT ␒ྕ PTP 30 㘄 䠄10 㘄㽢3䠅 1179422010101 PTP 100 㘄 䠄10 㘄㽢10䠅 1179422010102 17䠊 ಖ㝤⤥ୖ䛾ὀព 䝟䞊䜻䞁䝋䞁䛿ᣦᐃ㞴䛾䛯䜑䚸ㄆᐃ䜢ཷ䛡䛯ᝈ⪅䛿་⒪㈝䛾⮬ᕫ㈇ᢸศ䛾୍㒊䚸䜎䛯䛿 㢠䛜බ㈝㈇ᢸ䛥䜜䜛䚹 53 䊪䠊ᩥ⊩ 䠍䠊 ᘬ⏝ᩥ⊩ 1) Knoll J. et al.: MTA V. 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J. et al.: ᮍⓎ⾲ 䠎䠊 䛭䛾䛾ཧ⪃ᩥ⊩ ヱᙜ㈨ᩱ䛺䛧䚹 䠏䠊 ᩥ⊩ㄳồඛ ᘬ⏝ᩥ⊩䛻グ㍕䛾♫ෆ㈨ᩱ䛻䛴䛝䜎䛧䛶䜒ୗグ䛻䛤ㄳồ䛟䛰䛥䛔䚹 䜶䝣䝢䞊ᰴᘧ♫ ་⸆Ꮫ⾡㒊 䛈580-0011 㜰ᗓᯇཎᕷすሯ 1 ┠ 3 ␒ 40 ྕ TEL䠖0120-545-427 FAX䠖0120-728-093 56 䊫䠊ཧ⪃㈨ᩱ 䛺እᅜ䛷䛾Ⓨ≧ἣ䠄2010 ᖺ䠅 ㈍ ྡ ♫ ྡ ᢎ ㄆ ᪥ ᙧ ྵ 㔞 䝝䞁䜺䝸䞊 䜲䜼䝸䝇 䝗䜲䝒 䝣䝷䞁䝇 䜰䝯䝸䜹 Jumex Eldepryl Movergan Déprényl Eldepryl ㈍䠖Sanofi aventis 〇㐀䠖Chinoin Orion Orion Laboratoire HRA Pharma Somerset 1980 ᖺ 3 ᭶ 14 ᪥ 1982 ᖺ 8 ᭶ 12 ᪥ 1986 ᖺ 9 ᭶ 30 ᪥ 1987 ᖺ 12 ᭶ 4 ᪥ 1989 ᖺ 6 ᭶ 5 ᪥ 㘄 㘄 㘄 㘄 䜹䝥䝉䝹 5mg 5mg䚸10mg 5mg䚸10mg 5mg 5mg 䛔䛟䛴䛛䛾⚄⤒ኚᛶ ᝈ䠄䝟䞊䜻䞁䝋䞁䚸䜰 䝹䝒䝝䜲䝬䞊䠅䛾 ⒪䛻⏝䛷䛝䜛䚹 䝉䝺䜼䝸䞁䛿䝟䞊䜻䞁 䝋䞁䜒䛧䛟䛿ೃᛶ 䛾䝟䞊䜻䞁䝋䝙䝈䝮䛾 ⒪䛻㐺ᛂ䛩䜛䚹 ᮏ䛿䝺䝪䝗䝟䠄⬺Ⅳ 㓟㓝⣲㜼ᐖ䜢ే⏝ 䜒䛧䛟䛿ే⏝䛧䛺䛔䠅䛾 ᚲせᛶ䜢㐜䜙䛫䜛䛯䜑 䛾༢⊂⒪ἲ䚸䜒䛧䛟䛿 䝺䝪䝗䝟䛾⿵ຓ䠄⬺ Ⅳ㓟㓝⣲㜼ᐖ䜢ే ⏝䜒䛧䛟䛿ే⏝䛧䛺䛔䠅 䛸䛧䛶⏝䛔䛶䜒䜘䛔䚹 䝟䞊䜻䞁䝋䞁䛾⒪ ⏝䚹ᮏᝈ䛻⨯ᝈ䛧䛶 䛔䜛䛸᭱ึ䛻デ᩿䛥䜜 䛯䛸䛝䛛䜙䚸Movergan 䜢༢⊂⒪ἲ䛸䛧䛶䚸䜎 䛯䛿䝺䝪䝗䝟䠄ᮎᲈᛶ 䛾⬺Ⅳ㓟㓝⣲㜼ᐖ 䜢ྵ᭷䛧䛺䛔䠅䛸䛾ే ⏝䛷⏝䛔䜛䛣䛸䛜䛷䛝 䜛䚹 䝟䞊䜻䞁䝋䞁⒪䠖 䠉༢⊂⒪ἲ䠖Ẽ䛾ึ ᮇ䛻䛚䛔䛶䛿䚸䝉䝺䜼 䝸䞁䛿䝗䝟⒪䛾ᑟධ 䜢ᘏ㛗䛩䜛䛣䛸䛜ྍ⬟ 䛷䛒䜛䚹 䠉䝺䝪䝗䝟䛸䝗䝟⬺Ⅳ 㓟 㓝 ⣲ 㜼 ᐖ 䛸 䛾ే ⏝䠖 䠉 䝉䝺 䜼䝸 䞁䛿 䝺䝪 䝗 䝟䛾స⏝䜢ᙉ䜑䜛䛣䛸 䛻䜘䜚䚸䝺䝪䝗䝟⏝㔞䜢 ῶ䜙䛩䛣䛸䛜ྍ⬟䛷䛒 䜛䚹 䠉end of dose ≧ኚ ື䛾ẁ㝵䛷䚸䝉䝺䜼䝸 䞁䛿䝗䝟⒪䛾ຠᯝ䜢 ᘏ㛗䛥䛫䜛䚹 Eldepryl 䛿䝺䝪䝗䝟/ 䜹䝹䝡䝗䝟䛻䜘䜛⒪ 䜢ཷ䛡䛶䛚䜚䚸䛣䛾 ⒪䛻 ᑐ䛩 䜛 ᛂᛶ䛜 ᝏ䛧䛶䛔䜛䝟䞊䜻䞁 䝋䞁ᝈ⪅䛻ే⏝ᢞ 䛩䜛䚹䝺䝪䝗䝟⒪ 䜢ే⏝䛧䛶⾜䜟䛺䛔ሙ ྜ䛻䝉䝺䜼䝸䞁䛻䛿᭷ ┈䛺స⏝䛜䛒䜛䛸䛔䛖 䛣䛸䜢♧䛧䛯䝁䞁䝖䝻䞊 䝹ヨ㦂䛻䜘䜛䜶䝡䝕䞁 䝇䛿䛺䛔䚹 䛣䛾ᙇ䠄ᮏ䛾ే⏝ 䛻䜘䜛᭷ຠᛶ䠅䜢ᨭᣢ 䛩䜛ドᣐ䛿䝺䝪䝗䝟/䜹 䝹䝡䝗䝟䛾ᢞ䜢ཷ䛡 䛶䛔䜛ᝈ⪅䛻ᮏཪ 䛿䝥䝷䝉䝪䜢ຍ䛘䛯ຠ ᯝ䜢ẚ㍑䛧䛯↓సⅭ 䝁䞁䝖䝻䞊䝹⮫ᗋヨ 㦂䛷ᚓ䜙䜜䛶䛔䜛䚹 ᮏ䛿䝺䝪䝗䝟/䜹䝹䝡 䝗䝟䛾 1 ᪥⏝㔞䚸䇺off䇻 䛾㛫䚸⒪䛷Ⰻ䛟 䛺䛳䛯䛸䛔䛖ᝈ⪅䛾⮬ ᕫホ౯䛾せ䛺 3 䛴 䛾䜰䜴䝖䜹䝮䝯䝆䝱䞊 䠄ᣦᶆ䠅䛩䜉䛶䛻䛚䛔 䛶䚸䝧䞊䝇䝷䜲䞁䛛䜙䛾 ኚ䛜䝥䝷䝉䝪䜘䜚᭷ ព䛻䛩䛠䜜䛶䛔䛯䚹䛥 䜙䛻䚸ᮏ䛾᭷ຠᛶ䛿 ⒪䛾ᡂຌ䠄䛘䜀 end of dose 䛾↓ື䛾 ῶᑡ䚸ᡓ䛸ὶᾝ䛾ῶ ᑡ䚸ヰ䛸╔⾰䛾⬟ຊ 䛾 ᨵ ၿ ཬ䜃 ᢞ ๓䛸 ẚ ㍑ 䛧 䛯 Ṍ ⾜ ≧ ែ䛾 యⓗ䛺ᨵၿ䠅䛻㛵䛧 䛶䛾㡯┠䛻䛚䛔䛶䜒 ㄆ䜑䜙䜜䛯䚹 ຠ ⬟ ཪ 䛿 ຠ ᯝ 䠄⏝ἲཬ䜃⏝㔞䛿ḟ䝨䞊䝆䠅 57 䝝䞁䜺䝸䞊 䜲䜼䝸䝇 䝗䜲䝒 䝣䝷䞁䝇 䜰䝯䝸䜹 Jumex Eldepryl Movergan Déprényl Eldepryl 䝟䞊䜻䞁䝋䞁䛻䛚䛡 䜛㏻ᖖ 1 ᪥㔞䛿 10mg 䛷䚸ᮅᢞ䛒䜛䛔䛿ᮅ 䛸༗ᚋ᪩䛟䛻ศᢞ 䛩䜛䚹 䜰䝹䝒䝝䜲䝬䞊䛻䛚 䛔䛶䛿䚸㏻ᖖ䚸1 ᪥ 5mg ᮅᢞ䛛䜙㛤ጞ 䛧䚸1 ᪥ 10mg 䜎䛷ቑ 㔞䛩䜛䚹 ༢⊂⒪ἲ䚸䜒䛧䛟䛿 䝺 䝪䝗䝟䛛䝺䝪䝗䝟/ᮎᲈ ᛶ⬺Ⅳ㓟㓝⣲㜼ᐖ 䛾⿵ຓ䛸䛧䛶 1 ᪥ 10mg 䜢ᢞ䛩䜛䚹䝉 䝺䜼䝸䞁䛿 1 ᪥ 1 ᅇᢞ 䛸䛧䛶ᮅ䛻䚸䜒䛧䛟䛿 2 ᅇ䛻ศ䛡䛶ᮅ㣗䛸 㣗䛻 5mg 䜢᭹⏝䛩 䜛䚹䝉䝺䜼䝸䞁䛜䝺䝪䝗 䝟⒪ἲ䛻ຍ䛘䜙䜜䜛ሙ ྜ䚸ᖹᆒ 30%䜎䛷䛾䝺 䝪䝗䝟䛾ῶ㔞䛜ྍ⬟䛷 䛒䜛䚹 ᭱ึ䛾ᢞ䛿䚸㏻ᖖ䚸 1 ᪥䛒䛯䜚 5䡚10mg 䜢䚸༢⊂䚸䛒䜛䛔䛿ᮎ ᲈᛶ䛾⬺Ⅳ㓟㓝⣲㜼 ᐖྵ᭷䝺䝪䝗䝟䛸䛾 ే⏝䛷ጞ䜑䜛䚹1 ᪥䛒 䛯䜚᭱㧗 10mg 䜢⥔ᣢ 㔞䛸䛩䜛䜎䛷ኚ䛘䛶䛔 䛟 䛣 䛸 䛜 䛷 䛝 䜛 䚹 Movergan 䛿ᮅ 1 ᅇ䛾 ༢ᅇᢞ㔞䛷᭹⏝䛩 䜛䛛 2 ᅇ䛾ᢞ㔞䛻ศ 䛡䛶ᮅ䛸䠄ჶ䜎䛪䛻䚸 㣗ᚋ䠅᭹⏝䛩䜛䚹 䝺䝪䝗䝟䛸䛾ే⏝䛻㝿 䛧䛶䛿䚸䝺䝪䝗䝟䛾䛷䛝 䜛 䛰 䛡ప 䛔 ⏝ 㔞 䛷 㐺 ษ䛻䝁䞁䝖䝻䞊䝹䛥䜜 䛯≧䛻䛺䜛䜘䛖䛻䚸䝺 䝪䝗䝟䛾⏝㔞䜢ῶ㔞䛩 䜛䛣䛸䛜䛷䛝䜛䚹 䝟䞊䜻䞁䝋䞁ᝈ⪅䛻 䛚䛔䛶㏻ᖖ䛾᭷ຠ䛺 1 ᪥ᢞ㔞䛿䝉䝺䜼䝸䞁 ሷ㓟ሷ䛷 5䡚10mg 䛷 䛒䜛䚹 䠉༢⊂⒪ἲ䠖10mg/᪥ 䛷⒪䜢㛤ጞ䛩䜛䚹 䠉䝺䝪䝗䝟䛸ే⏝䠖 5mg/᪥䛷⒪䜢㛤ጞ 䛩䜛䚹 10mg 䛾ᢞ㔞䛷 1 ᅇ ᢞ䛾ሙྜ䚸ᮅ䛻᭹ ⏝䛩䜛䛣䛸䚹䝺䝪䝗䝟䛻 䝉䝺䜼䝸䞁䜢ే⏝䛩䜛䛸 䝺䝪䝗䝟䛾ᢞ㔞䜢ῶ 㔞䛩䜛䛣䛸䛻䛺䜛䚹䝺䝪 䝗 䝟䛾 ῶ 㔞 䛿 㐍 ⾜ ᛶ 䛷䛒䜚䚸ᝈ⪅䛾⮫ᗋᨵ ၿ䛸䛸䜒䛻ኚ䛧䚸3,4 ᪥ẖ䛻 10%䛪䛴ẁ㝵 ⓗ䛻 30%䛻㐩䛩䜛䛣䛸 䛜ྍ⬟䛷䛒䜛䚹 Eldepryl 䛿䝺䝪䝗䝟/ 䜹䝹䝡䝗䝟⒪䛾ᛂ ᛶ䛾ᝏ䛜ㄆ䜑䜙䜜 䛯䝟䞊䜻䞁䝋䞁ᝈ⪅ 䛻ᑐ䛧ే⏝ᢞ䜢䛩 䜛 䚹 Eldepryl 䛾 ᢎ ㄆ ⏝ἲ䞉⏝㔞䛿 10mg/᪥ 䛷䛒䜚䚸ᮅ㣗䛸㣗ᚋ 䛻ྛ䚻5mg 䜢ศᢞ 䛩䜛䚹䛣䜜௨ୖ䛾⏝ 㔞䛻䛚䛡䜛ຍⓗ䛺 ᭷┈ᛶ䛻䛴䛔䛶䛿ㄆ 䜑䜙䜜䛶䛔䛺䛔䚹䛺 䛚䚸䛣䜜௨ୖ䛾⏝㔞䛿 స⏝䛾༴㝤䛾ቑຍ 䛾䛯䜑㏻ᖖ䛿㑊䛡䜛䛣 䛸䚹 䝉䝺䜼䝸䞁⒪䛾 2䡚3 ᪥ᚋ䚸䝺䝪䝗䝟/䜹䝹䝡 䝗䝟⏝㔞䛾ῶ㔞䜢ヨ䜏 䜛䛣䛸䛜䛷䛝䜛䚹 ⡿ᅜෆ䛾䝥䝷䝉䝪䝁䞁 䝖䝻䞊䝹ヨ㦂䛻䛚䛔 䛶䚸䝉䝺䜼䝸䞁⒪䛻 䜚䛡䜙䜜䛯ᝈ⪅䛷 䝺䝪䝗䝟/䜹䝹䝡䝗䝟䛾 ⏝㔞䜢 10䡚30%ῶ㔞 䛩䜛䛣䛸䛜䛷䛝䛯䚹䝉䝺 䜼䝸䞁䛾⥅⥆⒪䛻䛚 䛔䛶䜒䚸䝺䝪䝗䝟/䜹䝹 䝡䝗䝟䛿䛥䜙䛻ῶ㔞ྍ ⬟䛻䛺䜛䜒䛾䛸ᛮ䜟䜜 䜛䚹 ㈍ ྡ ⏝ ἲ ཬ 䜃 ⏝ 㔞 䛯䛰䛧䚸ୗ⥺㒊 䛾ຠ⬟ཪ䛿ຠᯝ䚸⏝ἲཬ䜃⏝㔞䛻䛴䛔䛶䛿䚸᪥ᮏ䛾ᢎㄆ㡯䛸␗䛺䜛䚹 䊩䊢䠊ഛ⪃ 58
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