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Chronopharmacokinetics of Erlotinib and Circadian Rhythms of Related Metabolic Enzymes in Lewis Tumor-Bearing Mice

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Objective

The purpose of the current study was to investigate the effect of the dosing time on the pharmacokinetics of erlotinib and the circadian rhythms of the metabolism enzymes in tumor-bearing mice.

Methods

Female C57BL mice were randomly assigned to six groups. Erlotinib was orally administrated to the mice in each group at six different times of day. The plasma concentration of erlotinib was determined through a high-performance liquid-chromatographic assay, and the total mRNA was extracted from liver tissues to determine the expression of the mRNA of the related drug metabolism enzymes by qRT-PCR.

Results

The results indicated that AUC0–24 h and MRT0–24 h were the lowest in the 20:00 group (P < 0.01). T max of the 13 HALO (hour after light onset), 17 HALO and 21 HALO groups was higher than that of the 1 HALO and 5 HALO groups (P < 0.01). CL of the light-phase groups was lower than that of the dark-phase groups (P < 0.01). The peak value of C max appeared in the 5 HALO group (P < 0.01). The mRNA levels of Cyp3a11, Cyp3a13 and Cyp1a2 were generally higher during the afternoon and the dark phase.

Conclusion

Circadian rhythm plays a critical role in the pharmacokinetics of erlotinib in mice, and the mechanisms may be attributed to gene expression rhythms of drug-metabolizing enzymes in liver tissues.

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Acknowledgments

The authors would like to thank Mr. Jian-Xin Sun and Mr. Lin-Xiang Guo for proofreading this article.

Conflict of interest

The authors declare that they have no competing interests. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Pharmacy, No. 401 Hospital of Chinese People’s Liberation Army, Qingdao, Shandong, China

    Chun-Yan Wang, Song-Gang Ji, Xia Xu, Li-Yan Zhao & Ming-Chun Li

  2. Department of Pharmacy, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China

    Jiao Liu

  3. Department of Pharmacology, Medical College of Qingdao University, Qingdao, Shandong, China

    Liang Liu & Ping-Ping Lin

  4. Weifang Institute of Dermatology, Weifang, Shandong, China

    Le-Kun Liu

  5. School of Pharmacy, Fudan University, Shanghai, China

    Pei-Pei Wang

  6. Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

    Bin Zhang

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  1. Jiao Liu
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Correspondence to Ming-Chun Li.

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Liu, J., Wang, CY., Ji, SG. et al. Chronopharmacokinetics of Erlotinib and Circadian Rhythms of Related Metabolic Enzymes in Lewis Tumor-Bearing Mice. Eur J Drug Metab Pharmacokinet 41, 627–635 (2016). https://doi.org/10.1007/s13318-015-0284-3

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  • DOI: https://doi.org/10.1007/s13318-015-0284-3

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