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Different effects of dihydropyridine calcium channel antagonists on CYP3A4 enzyme of human liver microsomes

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Abstract

The present study investigated inhibitory effects of 1,4-dihydropyridines (1,4-DHPs) calcium channel antagonists (1,4-DHP-CCAs) on cytochromeP450 3A4 (CYP3A4) of human liver microsomes and further explored importance of 1,4-DHPs molecular structural descriptors. Partial Least Squares method was applied to probe the quantitative relationships between the 1,4-DHPs molecular structural descriptors and its inhibitory actions, which demonstrated that different 1,4-DHP-CCAs could inhibit CYP3A4 enzyme’s activity differently. The K i values of nicardipine, lercandipine, cilnidipine, nitrendipine, lacidipine, nifedipine, felodipine were 10.13, 10.17, 11.44, 23.90, 29.34, 29.06 and 32.64 μmol L−1, respectively. It is suggested that the 1,4-DHPs molecular structural descriptors are the most important for its inhibitory effects based on the quantitative structure–activity relationship (QSAR) formula. The LogP was positively correlated to the K i, whereas molecular weight and molecule volume were negatively correlated. It is concluded that analysis of K i of 1,4-DHPs derivatives on the CYP3A4 activity may apply for the QSAR formula at the initial stage of clinical application of new drugs.

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Acknowledgments

Project was supported by ChangZhou public health bureau guidance foundation project, Clinical Pharmacy Foundation of ChangZhou Siyao Pharmaceuticals Co., Ltd (cs20090902). The guidance from Professor YAO TongWei of College of Pharmaceutical Sciences, Zhejiang University is gratefully acknowledged by one of us.

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Authors and Affiliations

  1. Department of Pharmacy, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213000, China

    Zongling Xia, Mingli Wang, Sulan Zou & Rong Chen

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  1. Zongling Xia
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  2. Mingli Wang
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  3. Sulan Zou
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  4. Rong Chen
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Correspondence to Mingli Wang.

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Xia, Z., Wang, M., Zou, S. et al. Different effects of dihydropyridine calcium channel antagonists on CYP3A4 enzyme of human liver microsomes. Eur J Drug Metab Pharmacokinet 37, 211–216 (2012). https://doi.org/10.1007/s13318-011-0076-3

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  • DOI: https://doi.org/10.1007/s13318-011-0076-3

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