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Pharmacokinetics of 4-Hydroxybenzaldehyde in Normal and Cerebral Ischemia–Reperfusion Injury Rats Based on Microdialysis Technique

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

Abstract

Aim

4-Hydroxybenzaldehyde (4-HBd) is used for the treatment of headaches, dizziness, and convulsions. The objective of this study was to characterize the pharmacokinetics of 4-HBd in cerebral ischemia-reperfusion injury (CIRI) rats by microdialysis technology with high-performance liquid chromatography with diode-array detection (HPLC-DAD) and ultra-performance liquid chromatography–mass spectrometry (UPLC-MS).

Methods

Microdialysis was used to collect blood, feces, and urine of normal and CIRI model rats. Pharmacokinetic parameters were determined using HPLC-DAD and 4-HBd metabolites were determined using UPLC-MS.

Results

After gavage of 4-HBd in normal and middle cerebral artery occlusion/reperfusion (MCAO/R) rats, it was widely distributed to all tissues (heart, liver, spleen, lung, kidney, and brain) in both the equilibrium and elimination phases, and the distribution pattern was basically the same; the highest concentration was found in the brain. The absolute bioavailability of 4-HBd was 5.33%; however, after intragastric administration in normal and MCAO/R rats, fecal and urinary excretion of 4-HBd accounted for 0.02% and 0.01% and for 0.01% and 0.03% of the dosage, respectively. Furthermore, 4-HBd was rapidly metabolized into 4-hydroxybenzoic acid (4-HBA) after administration in both the control and MCAO/R groups. Compared with the control, the peak time of 4-HBd plasma concentration in the MCAO/R rats decreased from 10.67 min to 8.83 min, the area under the concentration-time curve decreased significantly, and the half-life increased from 31.81 min to 78.85 min.

Conclusions

The rapid absorption and low absolute bioavailability of 4-HBd by gavage in rats are followed by rapid and wide distribution to various tissues and organs, including the brain. The prototype drug is excreted in the feces and urine in low amounts, and it is metabolized to 4-HBA in large amounts in vivo; the pathological state of the MCAO/R model mainly affects its absorption degree and metabolism rate.

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Acknowledgements

The authors thank the help of Yunnan University of Traditional Chinese Medicine. All experiments were approved by the Institutional Ethical Committee on Animal Care and Experimentations of Yunnan University of Traditional Chinese Medicine ®-082018005) (Kunming, China). All reasonable efforts were made to minimize animal suffering.

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Author notes

  1. Chunping Xu, Jin Feng and Hang Sun contributed equally to this work.

Authors and Affiliations

  1. The Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, China

    Chunping Xu, Jin Feng, Hang Sun, Mingli Yan, Qian Yang, Xiaonan Zhou, Jianguang Yang, Fangyan He & Qing Lin

  2. College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine Kunming, 1076 Yuhua Street, Chenggong District, Kunming, 650500, Yunnan Province, China

    Fangyan He & Qing Lin

Authors
  1. Chunping Xu
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  2. Jin Feng
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  8. Fangyan He
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Corresponding authors

Correspondence to Fangyan He or Qing Lin.

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Funding

This work was supported by Yunnan Provincial Department of Science and Technology - Basic Research General Project (202001AT070138); Yunnan Provincial Department of Science and Technology - Joint Special Key Project of Traditional Chinese Medicine (202101AF070026); Yunnan Provincial Department of Science and Technology - Basic Research Special General Project (202101AT070264); Yunnan Provincial High-level Talents of Traditional Chinese Medicine (TCM) Discipline Reserve Talents Training Project and China National Natural Science Foundation Project (82360784).

Conflict of interest

The authors declare there are no conflicts of interest.

Ethics Approval

All experiments were approved by the Institutional Ethics Committee on Animal Care and Experimentations of Yunnan University of Traditional Chinese Medicine (R-06202074) (Kunming, China). All reasonable efforts were made to minimize animal suffering.

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Not applicable.

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Not applicable.

Availability of data and material

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

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Author contributions

Qing Lin, Fang-yan He designed the research; Chunping Xu, Jin Feng, Hang Sun and did the major experimental work and contributed in manuscript writing; Mingli Yan and Qian Yang analyzed the data; Xiaonan Zhou participated in part of the experiments; Jianguang Yang revised the paper.

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Xu, C., Feng, J., Sun, H. et al. Pharmacokinetics of 4-Hydroxybenzaldehyde in Normal and Cerebral Ischemia–Reperfusion Injury Rats Based on Microdialysis Technique. Eur J Drug Metab Pharmacokinet 49, 23–32 (2024). https://doi.org/10.1007/s13318-023-00863-3

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  • DOI: https://doi.org/10.1007/s13318-023-00863-3

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