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Effect of breviscapine on CYP3A metabolic activity in healthy volunteers

  • Clinical Trial
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Abstract

Objective

The purpose of this study was to investigate the influence of breviscapine on the pharmacokinetics of concomitantly administered midazolam (MID) and its associations with and effects on genetic polymorphism of the gene encoding cytochrome P450 3A5 (CYP3A5) in healthy volunteers.

Methods

The study group comprised 17 healthy volunteers who had been genotyped for CYP3A5*3 prior to start of the study. These volunteers were given daily doses of 120 mg (40 mg, three times a day) of breviscapine or a placebo for 14 days, followed by 7.5 mg midazolam (MID) on day 15. The plasma concentrations of MID and the metabolite 1-hydroxy-midazolam (1-OH-MID) were determined by ultra-performance liquid chromatography-mass spectrometry for up to 12 h after drug administration.

Results

The pharmacokinetics of MID and 1-OH-MID were significantly different between the breviscapine and placebo groups, with a point estimate for MID AUC(0–12) of 1.56 (90% confidence interval 1.26, 1.87). The pharmacokinetics of MID and 1-OH-MID were not different among the CYP3A5 genotype groups, regardless of whether MID was coadministered with breviscapine or with placebo.

Conclusions

These findings suggest that breviscapine inhibited the metabolism of CYP3A in the volunteers, with no interaction difference among the different CYP3A5 genotypes.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81241139, 81,360,511) and by Dali University.

Author information

Author notes

  1. Xuan Zhou and Yang-yang Gao contributed equally to this work.

Authors and Affiliations

  1. Institute of Pharmacy and Chemistry, Dali University, 32 Jia Shi Bo Ave, Dali, 671000, People’s Republic of China

    Xuan Zhou, Yang-yang Gao, Hai-zhu Zhang & Yong Lai

  2. Department of Pharmacy, The First Affiliated Hospital, Dali University, 32 Jia Shi Bo Ave, Dali, 671000, People’s Republic of China

    Xuan Zhou

  3. Dali Institute for Food and Drug Control, Biopharmaceutical Park, Dali, 671000, People’s Republic of China

    Jian-yong Hu

  4. Department of Cardiology, The First Affiliated Hospital, Dali University, 32 Jia Shi Bo Ave, Dali, 671000, People’s Republic of China

    Yu Dong

  5. Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, 32 Jia Shi Bo Ave, Dali, 671000, People’s Republic of China

    Yong Lai

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  1. Xuan Zhou
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  2. Yang-yang Gao
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Correspondence to Yong Lai.

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Zhou, X., Gao, Yy., Hu, Jy. et al. Effect of breviscapine on CYP3A metabolic activity in healthy volunteers. Eur J Clin Pharmacol 74, 37–44 (2018). https://doi.org/10.1007/s00228-017-2346-8

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  • DOI: https://doi.org/10.1007/s00228-017-2346-8

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