Involvement of a Cytochrome P4502D Subfamily in Human Liver Microsomal Bunitrolol 4-Hydroxylation

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概要

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• The oxidative metabolism of bunitrolol, an adrenergic β-receptor antagonist was examined in human liver microsomes fortified with an NADPH-generating system. The microsomal fractions (n=11) showed bunitrolol 4-hydroxylase activities, which correlated well with CYP2D6 contents (correlation coefficient, r=0.854), debrisoquine 4-hydroxylase (r=0.953) and imipramine 2-hydroxylase (r=0.976) activities. On the other hand, the bunitrolol 4-hydroxylase activity showed relatively poor correlations with CYP3A4 content (r=0.552) and testosterone 6β-hydroxylase activity (r=0.668). The bunitrolol 4-hydroxylase activity was significantly inhibited by quinidine, a selective inhibitor for CYP2D6. Polyclonal antibodies raised against rat liver microsomal cytochrome P450BTL, which is thought to belong to the CYP2D subfamily, effectively inhibited bunitrolol 4-hydroxylation. In contrast, polyclonal antibodies raised against human liver microsomal CYP3A4 did not show any inhibitory effect on the activity. These results suggest that CYP2D6 is involved in the bunitrolol 4-hydroxylase activity in human liver microsomes.

• 1994-06-15

著者

• 斎藤 徹

  Faculty Of Pharmaceutical Sciences Kanazawa University

• 桝渕 泰宏

  千葉大・院・薬

• 成松 鎮雄

  千葉大・薬

• 成松 鎮雄

  岡山大・薬・衛生化学

• 成松 鎭雄

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Suzuki T

  Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.

• 桝渕 泰宏

  Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University

• 鈴木 徳治

  Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University

• 細川 晋

  Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University

• 大森 栄

  Division of Pharmacy, School of Medicine, Chiba University Hospital

• 北田 光一

  Division of Pharmacy, School of Medicine, Chiba University Hospital

• 鈴木 徳治

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Suzuki T

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Saito Takako

  Research And Development Laboratories Maruho Co. Ltd.

• 細川 晋

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Suzuki Toshikazu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Masubuchi Y

  Laboratory Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Chiba Institute Of Scienqes

• Suzuki T

  Research Unit Of Pharmaceutics College Of Pharmacy Nihon University

• Narimatsu S

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

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