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Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia

  • Pharmacogenetics
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Abstract

Objective

This study investigated the relevance of the cytochrome P450 (CYP) 2D6 genotype to the adverse drug reactions (ADRs) of H1-antihistamines and the level of sedation.

Methods

Japanese participants in a health screening program were asked to describe any past history of ADRs. Any subjects reporting ADRs induced by H1-antihistamines were then individually interviewed and defined as cases. Excessive daytime sleepiness, which had occurred in the cases as an H1-antihistamine-induced ADR, was assessed by the Epworth sleepiness scale (ESS), and an ESS score ≥12 was considered hypersomnia. CYP2D6*4, *5, *14, and *10 were genotyped by a panel of polymerase chain reaction techniques.

Results

Out of 2,074 participants, 100 cases (M:F = 37:63, mean age 51.9 ± 9.2 years) were eligible for analysis. The most common etiological drug was chlorpheniramine, which is the most frequently used H1-antihistamine in Japan. CYP2D6*10 allele and genotypes were more frequently found in the cases than in the healthy Japanese population in a large study (P < 0.005 and P = 0.039, respectively), but no difference was observed in the null alleles and genotypes. The ESS scores in 75 cases (M:F=25:50) who had experienced excessive daytime sleepiness were 9.5 ± 5.5 in men and 12.9 ± 6.1 in women (P < 0.001, cases vs. 34 subjects without symptoms; P = 0.001 men vs. women). The occurrence of hypersomnia increased as the number of CYP2D6 mutant alleles increased (P = 0.045).

Conclusion

The results suggest that the presence of the CYP2D6*10 allele is a risk factor for development of H1-antihistamine-induced ADRs in Japanese.

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Acknowledgment

We gratefully acknowledge the staff of the Japanese Red Cross Health Care Center for their assistance. The valuable cooperation of the students Mirai Hashimoto, Yoko Higa, Yuko Tomiyasu, Keigo Yurube, and Koji Yoko is also acknowledged. This work was supported by a grant-in-aid (no. 16590438-0) for scientific research from the Japanese Ministry of Education, Science, Sports and Culture, and by a grant-in-aid (no. 99-2) from the Organization for Pharmaceutical Safety and Research, Tokyo, Japan. The authors have identified no conflicts of interest in relation to this manuscript. This study complies with the current laws of Japan, where it was performed inclusive of ethics approval.

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Author notes

  1. Tetsuya Kamataki

    Present address: Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan

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

    Junji Saruwatari, Kazuyuki Ikeda, Masashi Nakao, Kentaro Oniki, Takayuki Seo & Kazuko Nakagawa

  2. Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    Masayuki Matsunaga & Tetsuya Kamataki

  3. Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan

    Shuichi Mihara & Toru Marubayashi

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  1. Junji Saruwatari
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Correspondence to Kazuko Nakagawa.

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Saruwatari, J., Matsunaga, M., Ikeda, K. et al. Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. Eur J Clin Pharmacol 62, 995–1001 (2006). https://doi.org/10.1007/s00228-006-0210-3

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  • DOI: https://doi.org/10.1007/s00228-006-0210-3

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