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'https://openalex.org/W2056277985', 'https://openalex.org/W2039860301', 'https://openalex.org/W2033644570', 'https://openalex.org/W2030975106', 'https://openalex.org/W2030371995', 'https://openalex.org/W2006346202', 'https://openalex.org/W1971896739', 'https://openalex.org/W1968063155'], 'abstract_inverted_index': {'クアゼパムならびにその代謝物M4およびM6について,ヒトにおける代謝酵素を明らかにするとともに,各種P450の活性に及ぼすこれら化合物の影響を検討した.代謝酵素の同定は9種の発現系P450(CYP1A2,CYP2A6,CYP2B6,CYP2C9,CYP2C19,CYP2D6,CYP2E1,CYP3A4およびCYP4A11)を用いてそれぞれの代謝反応に関与するP450分子種を検索した.また代謝に関与する主要なP450分子種を明らかにするため,ヒト肝ミクロソームを酵素源としてP450抗体およびP450抗血清を用いた阻害試験を行った.さらにクアゼパムからM4の代謝反応に関してはFMOの関与についても検討した.その結果,クアゼパムからM4への代謝にはCYP2C9およびCYP3A4の2分子種が関与することを明らかにした.また本代謝反応にFMOの関与はなかった.M4からM5への代謝はCYP3A4が,M4からM6への代謝は主としてCYP2C9およびCYP3A4が触媒することを明らかにした.さらにM6からM7への代謝はCYP3A4が触媒することを明らかにした.次にクアゼパム,M4およびM6がヒトの薬物代謝に関与する主要なP450(CYP1A2,CYP2A6,CYP2C9,CYP2C19,CYP2D6およびCYP3A4)による代謝に及ぼす影響,すなわち発現系P450を酵素源として各P450の指標酵素活性に及ぼす影響を評価した.その結果,検討したいずれのP450分子種に対してもクアゼパム,M4およびM6はほとんど影響を及ぼさないことを明らかにした.': 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