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The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects

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

Abstract

Purpose

Codeine is an analgesic drug acting on μ-opioid receptors predominantly via its metabolite morphine formed almost exclusively by CYP2D6. Genetic polymorphisms in CYP2D6 are associated with diminished pain relief and/or severe opioid side effects. In Chinese individuals, CYP2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the effect of this allele on the pharmacokinetics of codeine and its metabolites.

Method

A blood sample was collected from healthy Mongolian volunteers for CYP2D6 genotyping using a PCR-RFLP assay. A pharmacokinetic study was then carried out in three groups with CYP2D6*1/*1 (n = 10), CYP2D6*1/*10 (n = 10) and CYP2D6*10/*10 (n = 9) genotypes by collecting serial blood samples for determination of plasma levels of codeine and its metabolites, morphine, morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) before and after a single 30-mg oral dose of codeine phosphate. Codeine and its metabolites were measured by LC-MS/MS.

Results

No significant differences were observed in the pharmacokinetic parameters of codeine in the three genotype groups. However, the C max and AUC0-∞ of morphine, M3G and M6G were significantly different between the study groups (P < 0.05). Compared with the *1/*1 group, the AUC0-∞ for morphine in the *1/*10 and *10/*10 groups decreased by ratios (95 % CI) of 0.93 (0.26–1.59) and 0.494 (0.135–0.853) respectively. Corresponding ratios for M3G were 0.791 (0.294–1.288) and 0.615 (0.412–0.818) and for M6G were 0.643 (0.39–0.957) and 0.423 (0.267–0.579).

Conclusion

This study demonstrates that the CYP2D6*10 allele plays an important role in the pharmacokinetics of the O-demethylated metabolites of codeine after oral administration.

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Acknowledgments

We would like to express our gratitude to the study participants, to Professor J. Paul Fawcett of University of Otago and to Professor Jingkai Gu of Jilin University for their excellent technical assistance.

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Authors and Affiliations

  1. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, China

    Xiujun Wu & Jing Lv

  2. Department of Pharmacy, Shenyang Northern Hospital, Shenyang, 110016, China

    Xiujun Wu & Tao Guo

  3. Economic and Technological Development Zone Public Security Bureau of Shenyang, Shenyang, 110021, China

    Li Yuan

  4. School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China

    Jinliang Zuo

Authors
  1. Xiujun Wu
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  2. Li Yuan
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  3. Jinliang Zuo
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  4. Jing Lv
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  5. Tao Guo
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Corresponding author

Correspondence to Tao Guo.

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Wu, X., Yuan, L., Zuo, J. et al. The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects. Eur J Clin Pharmacol 70, 57–63 (2014). https://doi.org/10.1007/s00228-013-1573-x

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  • DOI: https://doi.org/10.1007/s00228-013-1573-x

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