Inhibitory Effects of Nicardipine to Cytochrome P450 (CYP) in Human Liver Microsomes

• Nakamura Katsunori

  Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences

• Ariyoshi Noritaka

  Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences

• Iwatsubo Takafumi

  Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Fukunaga Yasuhisa

  Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Higuchi Saburou

  Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Itoh Kunio

  Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd.

• Shimada Noriaki

  Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd.

• Nagashima Kazuo

  Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine

• Yokoi Tsuyoshi

  Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences

• Yamamoto Koujirou

• Horiuchi Ryuya

• Kamataki Tetsuya

  Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences

抄録

To anticipate drug–drug interactions by nicardipine in vivo, cytochrome P450 (CYP) forms responsible for the metabolism of nicardipine and inhibition of CYP-dependent drug metabolism by nicardipine were investigated. Microsomes of human B-lymphoblastoid cells expressing each human CYP form were used for the metabolism of nicardipine. Inhibitory effects of nicardipine on drug metabolism were studied using human liver microsomes. CYP2C8, CYP2D6 and CYP3A4 were identified as major CYP forms for the metabolism of nicardipine in human liver microsomes. Nicardipine strongly inhibited two-pathways of triazolam hydroxylation both catalyzed by CYP3A4. Comparison of three Ca²⁺ antagonists, nicardipine, nifedipine, and diltiazem revealed that only nicardipine showed such a strong inhibitory potency on the typical CYP2D6-catalyzed drug metabolism. Furthermore, nicardipine inhibited other reactions catalyzed by CYP1A, CYP2A6, CYP2C8, CYP2C9 and CYP2C19 with K_i values ranging from 1.1 to 29.4 μM. In conclusion, nicardipine was a relatively potent inhibitor of human CYP2D6, CYP3A4 and CYP2C (especially for CYP2C8 and CYP2C19) in vitro, suggesting that drug–drug interactions between nicardipine and other drugs metabolized mainly by these CYP forms appear to occur in vivo.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 28 (5), 882-885, 2005

  公益社団法人 日本薬学会

キーワード

• Ca²⁺ blocker
• diltiazem
• drug–drug interaction
• nifedipine

詳細情報

• CRID: 1390282679603461888
• NII論文ID: 10016663470
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.28.882
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 7304695
• PubMed: 15863898
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7304695
• Web Site: http://www.jstage.jst.go.jp/article/bpb/28/5/28_5_882/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2006261994
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可