Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Inhibitory Effects of Nicardipine to Cytochrome P450 (CYP) in Human Liver Microsomes
Katsunori NakamuraNoritaka AriyoshiTakafumi IwatsuboYasuhisa FukunagaSaburou HiguchiKunio ItohNoriaki ShimadaKazuo NagashimaTsuyoshi YokoiKoujirou YamamotoRyuya HoriuchiTetsuya Kamataki
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2005 Volume 28 Issue 5 Pages 882-885


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 Ki 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.

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© 2005 The Pharmaceutical Society of Japan
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