Dose dependency of brain histamine H1 receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin
Dose dependency of brain histamine H1 receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin
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DOI：
10.1002/hup.1051
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发表时间：
2009-10-01
影响因子：
1.7
通讯作者：
Yanai, Kazuhiko
中科院分区：
文献类型：
--
作者：
Tashiro, Manabu;Kato, Motohisa;Yanai, Kazuhiko
目的：抗组胺药的镇静作用强度可以用正电子发射断层扫描（PET）来评估。本研究的目的是测量口服西替利嗪后组胺H-1受体（H1 R）的占有率方法15名健康男性志愿者，分别给予10 mg和20 mg两种不同剂量的地塞米松，观察其剂量依赖性（年龄范围，20-35岁）分为3个亚组，分别在单次口服西替利嗪10 mg（n = 5）和20 mg（n = 5）后进行研究或羟嗪30 mg（n = 5），使用PET与C-11-多塞平。每例受试者在安慰剂给药后也接受扫描。结合电位和H1 RO值计算在前额叶和前扣带皮层。结果西替利嗪10 mg、20 mg和羟嗪30 mg在前额叶和扣带皮层的平均H1 RO分别为12.6%、25.2%和67.6%。羟嗪30 mg的H1 RO与主观嗜睡度相关性良好（p < 0.001），而西替利嗪10和20 mg的H1 RO与主观嗜睡度无相关性。西替利嗪10 mg，其低H1 RO，因此最小的镇静，可以更安全地使用比西替利嗪20 mg治疗各种过敏性疾病。版权所有（c）2009约翰威利父子有限公司。
Aims The strength of sedation due to antihistamines can be evaluated using positron emission tomography (PET). The purpose of the present study is to measure histamine H-1 receptor (H1R) occupancy following oral administration of cetirizine (10 and 20 mg) in order to examine dose dependency.Methods Fifteen healthy male volunteers (age range, 20-35 years) were divided into 3 subgroups and were studied following single oral administration of cetirizine at 10 mg (n = 5) and 20 mg (n = 5) or hydroxyzine at 30 mg (n = 5) using PET with C-11-doxepin. Each subject was scanned also following the administration of placebo. Binding potential and H1RO values were calculated in the prefrontal and anterior cingulate cortices. Subjective sleepiness was also measured, and the correlation to H1RO was examined for each antihistamine.Results The averaged H1ROs of cetirizine 10 mg, 20 mg, and hydroxyzine 30 mg in the prefrontal and cingulate cortices was 12.6%, 25.2%, and 67.6%, respectively. The H1RO of hydroxyzine 30 mg correlated well with subjective sleepiness (p < 0.001); however, those of cetirizine 10 and 20 mg showed no correlation with subjective sleepiness.Conclusion It was demonstrated that the brain penetration of orally administered cetirizine was dose-dependent. Cetirizine 10 mg, with its low H1RO and thus minimal sedation, could be more safely used than cetirizine 20 mg for the treatment of various allergic disorders. Copyright (c) 2009 John Wiley & Sons, Ltd.