Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver microsomes

Katsunori Nakamura, Noritaka Ariyoshi, Takafumi Iwatsubo, Yasuhisa Fukunaga, Saburou Higuchi, Kunio Itoh, Noriaki Shimada, Kazuo Nagashima, Tsuyoshi Yokoi, Koujirou Yamamoto, Ryuya Horiuchi, Tetsuya Kamataki

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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 29.4μM. 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.

Original languageEnglish
Pages (from-to)882-885
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Issue number5
Publication statusPublished - May 2005
Externally publishedYes


  • Ca blocker
  • Diltiazem
  • Drug-drug interaction
  • Nifedipine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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