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Effects of the Chinese herbal formula “Zuojin Pill” on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype.

Methods

A pharmacokinetics interaction study was carried out in three groups with CYP2D6*1/*1 (n = 6), CYP2D6*1/*10 (n = 6), and CYP2D6*10/*10 (n = 6) genotypes. Each participant received a single oral dose of dextromethorphan (15 mg) followed by Zuojin Pill (3 g twice daily) for 7 days, and received 3 g Zuojin Pill with 15 mg dextromethorphan in the last day. Blood samples (0–24 h) and urine samples (0–12 h) were collected at baseline and after the administration of Zuojin Pill, and the samples’ concentration of dextromethorphan and its main metabolite dextrorphan was determined.

Results

Compared to baseline values, co-administration of Zuojin Pill (3 g twice daily) for 7 days increased the AUC0-24 of dextromethorphan [mean (90 % CI)] by 3.00-fold (2.49∼3.61) and 1.71-fold (1.42∼2.06), and decreased oral clearance(CL/F) by 0.27-fold (0.2-0.40) and 0.57-fold (0.48-0.67) in the participants with CYP2D6*1/*1 and CYP2D6*1/*10 genotypes, respectively. In contrast, no significant change was observed in these pharmacokinetic parameters of the participants with CYP2D6*10/*10 genotype.

Conclusion

These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10 groups than CYP2D6 *10/*10 group.

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Acknowledgments

This work was supported by the National Natural Science Foundation of the People’s Republic of China (Grant 81173118), the National Key New Drug Creation Special Programme (Grant 2012ZX09303009-001), and the Shanghai Key Lab of Traditional Clinical Medicine (Grant C10dZ2220200).

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    Authors and Affiliations

    1. Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People’s Republic of China

      Furong Qiu, Songcan Liu, Ping Miao, Jin Zeng, Leilei Zhu, TongFang Zhao, Yujie Ye & Jian Jiang

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    1. Furong Qiu
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    Correspondence to Furong Qiu or Jian Jiang.

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    Furong Qiu and Songcan Liu contributed equally to this work.

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    Qiu, F., Liu, S., Miao, P. et al. Effects of the Chinese herbal formula “Zuojin Pill” on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype. Eur J Clin Pharmacol 72, 689–695 (2016). https://doi.org/10.1007/s00228-016-2048-7

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