Lee Ho-Won, Lee Hae Won, Park Dae Jin, Moon Sung Ok, Ahn Ju Hee, Kim Mi Jin, Kim Sung-Doo, Kim Ji-Eun, Yoon Young-Ran
Kyungpook National University Hospital, Department of Neurology, 50 Samduk-dong 2 Ga, Jung-gu, Daegu, 700-721, Korea.
Expert Opin Pharmacother. 2008 Jul;9(10):1655-65. doi: 10.1517/14656566.9.10.1655.
To compare the effects of a first-generation antihistamine, chlorpheniramine, with those of the second-generation antihistamine, fexofenadine, at steady-state, on nocturnal sleep architecture in healthy Korean volunteers using polysomnography and the Multiple Sleep Latency Test. We evaluated whether a genetic polymorphism of multi-drug resistance 1 gene (MDR1) could produce variations in pharmacokinetic and pharmacodynamic parameters of fexofenadine.
DESIGN/METHODS: Ten healthy male volunteers received one capsule of fexofenadine 180 mg once each morning or chlorpheniramine 6 mg (2 mg in the morning and 4 mg after 12 h) for 3 days, in a single-site, randomized, double-blind, two-treatment, multiple-dosing, two-way crossover study, with a washout period of 7 days. Overnight polysomnography was measured on the second night of the treatment period. The Multiple Sleep Latency Test was carried out the next morning. Blood samples were taken for the assessment of fexofenadine pharmacokinetics and MDR1 genotyping on the third day.
Compared with baseline and fexofenadine, chlorpheniramine significantly increased the latency in rapid eye movement (REM) sleep, with no significant decrease in the percentage of REM sleep. No significant change in latency for REM sleep or percentage REM sleep after dosing with fexofenadine was observed. There was no significant change in the daytime sleepiness with fexofenadine and chlorpheniramine. The effects of MDR1 genotypes and haplotypes on the pharmacokinetics and pharmacodynamics of fexofenadine were not significant.
Our findings suggest that fexofenadine and chlorpheniramine at steady-state have no significant effect on nocturnal sleep variables and daytime sleepiness, when compared to baseline.
采用多导睡眠图和多次睡眠潜伏期试验，比较第一代抗组胺药氯苯那敏与第二代抗组胺药非索非那定在稳态时对健康韩国志愿者夜间睡眠结构的影响。我们评估了多药耐药1基因（MDR1）的基因多态性是否会导致非索非那定的药代动力学和药效学参数出现差异。
设计/方法：在一项单中心、随机、双盲、双治疗、多剂量、双向交叉研究中，10名健康男性志愿者每天早晨服用1粒180mg非索非那定胶囊，或服用6mg氯苯那敏（早晨2mg，12小时后4mg），持续3天，洗脱期为7天。在治疗期的第二个晚上进行整夜多导睡眠图测量。第二天早晨进行多次睡眠潜伏期试验。在第三天采集血样，用于评估非索非那定的药代动力学和MDR1基因分型。
与基线和非索非那定相比，氯苯那敏显著增加了快速眼动（REM）睡眠的潜伏期，而REM睡眠百分比没有显著下降。服用非索非那定后，REM睡眠潜伏期或REM睡眠百分比没有显著变化。非索非那定和氯苯那敏对白天嗜睡情况没有显著影响。MDR1基因型和单倍型对非索非那定药代动力学和药效学的影响不显著。
我们的研究结果表明，与基线相比，稳态时的非索非那定和氯苯那敏对夜间睡眠变量和白天嗜睡情况没有显著影响。
