Analysis of the individual difference in the sedation with the antihistamine

抗组胺药镇静个体差异分析

• 批准号: 19790133
• 负责人: KOHYAMA Noriko
• 金额: $ 2.43万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19790133/
• 关键词: 臨床薬理学; 薬物動態学; 眼球運動解析; 抗ヒスタミン薬; 薬剤反応性; トランスポーター; 薬物動態; 血液脳関門; 精神薬理学; 薬理遺伝学; ファーマコゲノミックス; 遺伝子多型

We evaluated the sedative effect of histamine H1 receptor antagonists (H1-antagonists) by eye movement analysis. Trial 1; A randomized, double-blind, three-way crossover study was performed in six healthy male volunteers. Subjects took d-chlorpheniramine 1, 2, or 4 mg in each period. Trial 2; A randomized, double-blind, two-way crossover study was performed in ten healthy volunteers. Subjects took 2 mg d-chlorpheniramine or 10 mg ebastine. The sedative effects of H1-antagonists were assessed by visual analogue scale (VAS) and saccadic peak velocity (SPV) obtained from eye movement analysis. Plasma concentrations of chlorpheniramine and carebastine were analyzed using HPLC. The values of SPV were correlated with VAS “alertness scores". Maximal effects on SPV were correlated with the area under the concentration-time curve of chlorpheniramine. Therefore, we suggest that SPV is a quantitative marker of the sedative effects of H1-antagonists. In trial 2, both d-chlorpheniramine and ebastine reduced SPV significantly compared with before administration, although the H1-antagonists had a little effect on VAS. Thus, the eye movement analysis may be a useful tool for evaluation the unconscious sedative effects of H1-antagonists.

我们通过眼动分析评估了组胺H1受体拮抗剂（H1-抗逆转肌曲）的镇静作用。试验1;在六名健康的男性志愿者中进行了一项随机的双盲，三向跨界研究。受试者在每个时期服用D-氯苯胺1、2或4 mg。试验2;在十名健康志愿者中进行了一项随机的双盲，双向跨界研究。受试者服用2 mg D-氯苯胺或10 mg eBastine。通过视觉模拟量表（VAS）和sacadic峰速度（SPV）评估了H1-抗逆转录病毒学家的镇静作用。使用HPLC分析了氯苯胺和Carebastine的血浆浓度。 SPV的值与VAS“机敏得分”相关。对SPV的最大影响与氯苯浓度曲线下的面积相关。因此，我们建议SPV是H1抗逆转录病毒学家的镇静作用的定量标记。在试验2中，与给药前相比，D-氯苯甲胺和ebastine都显着降低了SPV，尽管H1抗逆转肌师对VAS的影响很小。这是眼动分析可能是评估H1抗逆转录病毒学家的无意识镇静作用的有用工具。