Inhibitory Effects of Nicardipine to Cytochrome P450 (CYP) in Human Liver Microsomes
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- Nakamura Katsunori
- Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences
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- Ariyoshi Noritaka
- Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences
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- Iwatsubo Takafumi
- Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
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- Fukunaga Yasuhisa
- Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
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- Higuchi Saburou
- Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
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- Itoh Kunio
- Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd.
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- Shimada Noriaki
- Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd.
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- Nagashima Kazuo
- Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine
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- Yokoi Tsuyoshi
- Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences
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- Kamataki Tetsuya
- Laboratory of Drug Metabolism, Hokkaido University Graduate School of Pharmaceutical Sciences
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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 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.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 28 (5), 882-885, 2005
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679603461888
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- NII Article ID
- 10016663470
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 7304695
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- PubMed
- 15863898
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed