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Comparison of the Pharmacokinetic Profiles of Ceftriaxone Used Alone and Combined with Danhong Injection in Old Rats

European Journal of Drug Metabolism and Pharmacokinetics volume 44, pages 505–517 (2019)Cite this article

Abstract

Background and Objectives

Danhong injection is the most commonly prescribed adjuvant drug applied for the treatment of cardiovascular and cerebrovascular diseases in China. Ceftriaxone is usually prescribed along with Danhong injection to elderly patients with complications. However, the pharmacokinetic interactions between these two medications have not been investigated. The aim of this study was to investigate whether Danhong injection influences the pharmacokinetic profile of ceftriaxone in old rats when these two medications are used in combination.

Methods

The animal experiment protocol was designed according to the clinical data. Ten-month-old male Sprague–Dawley (SD) rats were dosed with ceftriaxone through intravenous administration for 1 or 7 days in the presence or absence of Danhong injection. The combinations were divided into 1-day, 7-day, and 14-day combined-treatment groups in which Danhong injection was administered for 1, 7, or 14 days and ceftriaxone was given for 1, 7, or 7 days, respectively. The plasma concentration of ceftriaxone was determined by ultrahigh performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC–TQ–MS) on a BEH C18 column with a mobile phase consisting of acetonitrile and 0.4% formic acid–water. The chromatographic method was validated and found to be simple, rapid, and stable.

Results

Danhong injection significantly increased the plasma clearance of and decreased systemic exposure to ceftriaxone. In the 1-day combined-treatment group, the plasma clearance of ceftriaxone increased by 52.69%, and the area under the concentration–time curve (AUC) of ceftriaxone was decreased by 32.54% (P < 0.01). In the 7-day combined-treatment group, the rate of plasma clearance increased by 52.49% and the area under the concentration–time curve decreased by 31.15% (P < 0.01). For the 14-day combined-treatment group, the plasma clearance of ceftriaxone increased by 26.73%, and the area under the concentration–time curve decreased by 21.44% (P < 0.05).

Conclusions

In old male rats, systemic exposure to ceftriaxone decreased when used concomitantly with Danhong injection, which may be because Danhong injection increased the plasma clearance of ceftriaxone. Further investigations should be carried out to clarify the mechanism for the influence of Danhong injection on the pharmacokinetics of ceftriaxone.

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Acknowledgements

We would like to thank Dr. Xiaoxiao Wang for assistance with the data mining of the statistics on the concomitant use of medications with Danhong injection. We gratefully acknowledge Prof. J. A. Duan and Prof. W. Z. Ju for their supervision. We also thank Prof. Z. S. Tang and Prof. B. C. Zhao for their technical and financial support.

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Affiliations

  1. The Department of Pharmacy, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155, Hanzhong Road, Nanjing, 210029, People’s Republic of China

    Qian Zhang, Guoliang Dai, Lijing Zhu, Shufen He, Yang Zong & Wenzheng Ju

  2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Nanjing, 210046, People’s Republic of China

    Qian Zhang, Jianming Guo, Jianping Li & Jinao Duan

  3. Shanxi University of Traditional Chinese Medicine, Xianyang, People’s Republic of China

    Zhishu Tang

  4. Buchang Pharma, Xi’an, People’s Republic of China

    Buchang Zhao

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  1. Qian Zhang
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Correspondence to Wenzheng Ju or Jinao Duan.

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Funding

This work was financially supported by the National Basic Research Program of China (973 Program; 2011CB505300, 2011CB505303), the National Technology Major Project of China (2015ZX09501004001006), the Key Research Project in Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXM-2-2), the Science and Technology project of the Administration of Traditional Chinese Medicine of Jiangsu Province (YB2017018), and the Research Project and Innovation Program of graduate students at Jiangsu College and University (201510315064Y).

Conflict of interest

Q. Zhang, G. L. Dai, and W. Z. Ju were employees of the Affiliated Hospital of Nanjing University of Chinese Medicine, J. M. Guo, J. P. Li, and J. A. Duan were employees of Nanjing University of Chinese Medicine, and L. J. Zhu, S. F. He, and Y. Zong were employees of the Affiliated Hospital of Nanjing University of Chinese Medicine during the research reported in this paper. All of the authors declare that they have no potential conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. All procedures performed in studies involving animals were approved by animal care and use committees where the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Zhang, Q., Guo, J., Dai, G. et al. Comparison of the Pharmacokinetic Profiles of Ceftriaxone Used Alone and Combined with Danhong Injection in Old Rats. Eur J Drug Metab Pharmacokinet 44, 505–517 (2019). https://doi.org/10.1007/s13318-018-0530-6

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