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The effect of Shoseiryuto, a traditional Japanese medicine, on cytochrome P450s, N-acetyltransferase 2 and xanthine oxidase, in extensive or intermediate metabolizers of CYP2D6

  • Pharmacokinetics and Disposition
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Abstract

Objective

Shoseiryuto (TJ-19) contains eight herbal components, including Ephedra sinica, and has been used for treating asthma and allergic rhinitis in Asian countries for several centuries. In this study, we investigated the potential herb–drug interaction of TJ-19 in healthy volunteers and attempted to ascertain whether or not the interaction might be affected by the cytochrome P450 (CYP) 2D6 genotype.

Methods

We assessed the effect of TJ-19 on the activities of CYP1A2, CYP2D6, CYP3A, xanthine oxidase (XO), and N-acetyltransferase 2 (NAT2) in 37 healthy subjects. The subject pool consisted of 19 extensive metabolizers (EMs) with CYP2D6*Wild/*Wild, and 18 intermediate metabolizers (IMs) with CYP2D6*10/*10. The baseline activities of five enzymes were ascertained by their respective urinary metabolic ratios from an 8-h urine sample, after an oral 150-mg and 30-mg dose of caffeine and dextromethorphan were administrated, respectively. Thereafter, the subjects received 4.5 g of TJ-19 twice daily for 7 days, and underwent the same phenotyping test on postdose day 7.

Results

The activities of all enzymes examined did not differ before or after the 7-day administration of TJ-19. Consequently, the influence of the CYP2D6 genotype on the herb–drug interaction remained unsolved.

Conclusion

Our results indicate that TJ-19 at the generally recommended dosage is unlikely to cause pharmacokinetic interaction with co-administered medications primarily dependent on the CYP1A2, CYP2D6, CYP3A, XO, and NAT2 pathways for elimination.

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Acknowledgement

This work was partially supported by a Grant-in-aid (No.16590438-0) for scientific research from the Japanese Ministry of Education, Science, Sports and Culture. This study complies with the current laws of Japan. It was performed inclusive of ethics approval.

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Authors and Affiliations

  1. Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto, 862-0973, Japan

    Masashi Nakao, Yousuke Muramoto, Motoko Hisadome, Naoko Yamano, Mami Shoji, Junji Saruwatari & Kazuko Nakagawa

  2. Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Yumi Fukushima

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  1. Masashi Nakao
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  2. Yousuke Muramoto
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  3. Motoko Hisadome
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Correspondence to Kazuko Nakagawa.

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Nakao, M., Muramoto, Y., Hisadome, M. et al. The effect of Shoseiryuto, a traditional Japanese medicine, on cytochrome P450s, N-acetyltransferase 2 and xanthine oxidase, in extensive or intermediate metabolizers of CYP2D6. Eur J Clin Pharmacol 63, 345–353 (2007). https://doi.org/10.1007/s00228-006-0253-5

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  • DOI: https://doi.org/10.1007/s00228-006-0253-5

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