ヒスタミンＨ１受容体遮断薬ＰｒｏｍｅｔｈａｚｉｎｅおよびＨｏｍｏｃｈｌｏｒｃｙｃｌｉｚｉｎｅがＨａｌｏｐｅｒｉｄｏｌおよびＲｅｄｕｃｅｄ　Ｈａｌｏｐｅｒｉｄｏｌの定常状態血しょう濃度に与える影響について

• 鈴木 昭仁

  弘前大学医学部神経精神医学

書誌事項

タイトル別名

• Effects of Histamine H1 Receptor Antagonists Promethazine and Homochlorcyclizine on Steady-State Plasma Concentrations of Haloperidol and Reduced Haloperidol.

抄録

The purpose of this study was to clarify the effects of histamine H₁ receptor antagonists promethazine and homochlorcyclizine, which are reported to be cytochrome P450 2D6 (CYP2D6) inhibitors, on the steady-state plasma concentrations (C_ss) of haloperidol (HAL) and reduced haloperidol (RHAL). Twenty-one schizophrenic patients treated with HAL 12-36 mg/day received promethazine 150 mg/day (n=11) or homochlorcyclizine 60 mg/day (n=10) for at least one week. The changes in C_ss of HAL and RHAL were monitored before and during coadministration of promethazine or homochlorcyclizine and one week after the discontinuation. In 11 cases with promethazine coadministration, the C_ss of HAL was significantly higher during the coadministration period than that before the coadministration (p<0.01) or one week after the discontinuation (p<0.01) (before and during coadministration of promethazine and one week after its discontinuation: 13.3±11.0, 29.3±25.0, 16.6±15.1 ng/ml, respectively). The C_ss of reduced haloperidol was also significantly higher during the coadministration period than that before the coadministration (p<0.01) or one week after the discontinuation (p<0.05) (5.6±6.2, 9.5±13.7, 6.3±8.2 ng/ml). Likewise, in 10 cases with homochlorcyclizine coadministration, the C_ss of HAL was significantly higher during the coadministration period than before the coadministration (p<0.01) or one week after the discontinuation (p<0.05) (11.7±7.9, 16.5±8.4, 14.1±7.8 ng/ml), and the C_ss of RHAL was also significantly higher during the coadministration period than that before the coadministration (p<0.01) or one week after the discontinuation (p<0.05) (4.2±4.0, 7.4±5.8, 5.4±4.5 ng/ml). These results suggest that promethazine and homochlorcyclizine inhibit the metabolism of HAL and RHAL via inhibitory effects on CYP2D6 activity. Therefore, it is considered that the C_ss of HAL and RHAL are at least partly affected by the CYP2D6 activity.

収録刊行物

• 臨床薬理

  臨床薬理 29 (3), 517-523, 1998

  一般社団法人 日本臨床薬理学会

キーワード

• haloperidol
• reduced haloperidol
• promethazine
• homochlorcyclizine
• cyto-chrome P450 2D6

詳細情報

• CRID: 1390001205341565952
• NII論文ID: 10013843293
• NII書誌ID: AN0025404X
• DOI: 10.3999/jscpt.29.517
• ISSN: 18828272
• ISSN: 03881601
• Web Site: https://search.jamas.or.jp/link/ui/1998240448
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可