The effects of acute doses of fexofenadine, promethazine, and placebo on cognitive and psychomotor function in healthy Japanese volunteers
The effects of acute doses of fexofenadine, promethazine, and placebo on cognitive and psychomotor function in healthy Japanese volunteers
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DOI：
10.1016/s1081-1206(10)61824-8
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发表时间：
2003-04-01
影响因子：
5.9
通讯作者：
Hindmarch, I
中科院分区：
文献类型：
--
作者：
Ridout, F;Hindmarch, I
背景：跨文化代谢能力的遗传变异可能会减弱非索非那定对中枢神经系统的影响。目的：比较非索非那定和异丙嗪与安慰剂在日本志愿者体内的药效学。方法：在这项随机、交叉、双盲研究中，24名受试者接受单剂量非索非那定60 mg和120 mg、异丙嗪25 mg和安慰剂治疗，两次治疗之间有6天的洗脱期。客观测量包括临界闪烁融合、选择反应时间和补偿跟踪任务。线模拟评定量表评估自评镇静。快速视觉信息处理任务在基线和2小时时评估警觉性。结果：非索非那定与安慰剂在任何时间点的任何测试均无显著差异。相反，异丙嗪损害临界闪烁融合阈值（F[3,63] = 5.37, P = 0.0023）；增加了识别反应时间（F[3,63] = 13.63, P < 0.0001）和总反应时间（F[3,63] = 12.23, P < 0.0001）的选择反应时间测试成分；在代偿性跟踪任务中，跟踪精度降低（F[3,63] = 14.25, P < 0.0001），对周边刺激的反应时间增加（F[3,631] = 9.29, P < 0.0001）；在快速视觉信息处理任务测试中，有效反应数减少（F[3,63] = 14.86, P < 0.0001），反应时间缩短（F[3,631] = 12.02, P < 0.0001）；与安慰剂相比，镇静的主观评分受损（F[3,631 = 7.55, P = 0.0002）。结论：对异丙嗪损伤敏感的一系列试验未能显示非索非那定60和120 mg对认知或精神运动有任何负面影响。非索非那定在日本受试者中是一种本质上无损伤的抗组胺药。
Background: Genetic variations in cross-cultural metabolic capability may attenuate the lack of central nervous system effects of fexofenadine.Objective: To compare the pharmacodynamics of fexofenadine and promethazine versus placebo in Japanese volunteers.Methods: In this randomized, crossover, double-blind study, 24 subjects received single doses of fexofenadine 60 mg and 120 mg, promethazine 25 mg, and placebo, with a 6-day washout period between treatments. Objective measures included critical flicker fusion, choice reaction time, and a compensatory tracking task. A line analog rating scale evaluated self-rated sedation. A rapid visual information-processing task evaluated vigilance at baseline and at 2 hours.Results: Fexofenadine was not significantly different from placebo on any test at any timepoint. In contrast, promethazine impaired critical flicker fusion thresholds (F[3,63] = 5.37, P = 0.0023); increased recognition reaction time (F[3,63] = 13.63, P < 0.0001) and total reaction time (F[3,63] = 12.23, P < 0.0001) components of the choice reaction time test; reduced tracking accuracy (F[3,63] = 14.25, P < 0.0001) and increased reaction times to peripheral stimuli (F[3,631 = 9.29, P < 0.0001) in the compensatory tracking task; reduced the number of valid responses (F[3,63] = 14.86, P < 0.0001) and impaired reaction times (F[3,631 = 12.02, P < 0.0001) in the rapid visual information-processing task test; and impaired subjective ratings of sedation (F[3,631 = 7.55, P = 0.0002), compared with placebo.Conclusions: A battery of tests sensitive to impairment by promethazine failed to show any negative cognitive or psychomotor effects with fexofenadine 60 and 120 mg. Fexofenadine is an intrinsically non-impairing antihistamine in Japanese subjects.