Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia.
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.[1]References
- Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. Saruwatari, J., Matsunaga, M., Ikeda, K., Nakao, M., Oniki, K., Seo, T., Mihara, S., Marubayashi, T., Kamataki, T., Nakagawa, K. Eur. J. Clin. Pharmacol. (2006) [Pubmed]
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