Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver microsomes.
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Nakamura K, Ariyoshi N, Iwatsubo T, Fukunaga Y, Higuchi S, Itoh K, Shimada N, Nagashima K, Yokoi T, Yamamoto K, Horiuchi R, Kamataki T
Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver microsomes.
Biol Pharm Bull. 2005 May;28(5):882-5. doi: 10.1248/bpb.28.882.
- PubMed ID
- 15863898 [ View in PubMed]
- Abstract
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 Ca(2+) 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 microM. 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Nicardipine Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Nicardipine Cytochrome P450 2C8 Protein Humans UnknownSubstrateInhibitorDetails Nicardipine Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails Nicardipine Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
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