Dridi D, Ben Attia M, Reinberg A, Boughattas N A
Laboratoire de pharmacologie, faculté de médecine, Monastir, Tunisie.
Pathol Biol (Paris). 2005 May;53(4):193-8. doi: 10.1016/j.patbio.2004.07.014.
Cetirizine is a second generation histamine H(1) receptor antagonist used to provide symptomatic relief of allergic signs caused by histamine release. The aim of the study was to learn whether the survival and the motor incoordination (ataxia) side effect of cetirizine administration is dosing time-dependent.
A total of 240 male Swiss mice, 10 weeks of age were synchronized for 3 weeks by 12 h light (rest span)/12 h dark (activity span). Different doses of cetirizine were administered orally at fixed times during the day to determine both the sublethal (TD(50)) and lethal (LD(50)) doses, which were, respectively, 55 +/- 0.35 and 750 +/- 0.40 mg/kg. In the chronotoxicologic study a single dose of cetirizine (DL(50)) was administered to comparable groups of animals at six different circadian stages [1, 5, 9, 13, 17, 21 h after light onset (HALO)].
The survival was statistically significant dosing time-dependent (chi(2) = 16.73; P < 0.001). Drug dosing at 17 HALO resulted in 83.3% survival rate whereas drug dosing at 5 HALO was only 23.25%. Cosinor analysis revealed a statistically significant circadian (period approximately 24 h) rhythmic component in survival. Lowest (20%) and highest (88%) ataxia occurred when cetirizine was administered, respectively, at 17 and 5 HALO. Cosinor analysis revealed a statistically significant circadian (period approximately 24 h) rhythmic component in ataxia.
Our results reveal that the best safety is shown when cetirizine is administered in the middle of the dark (activity) span of the mice, since it produces some side effects: ataxia and hyperthermia. Taking into account of the hour administration of cetirizine, improves treatment efficacy and permit the best control of allergic diseases.
西替利嗪是一种第二代组胺H(1)受体拮抗剂，用于缓解组胺释放引起的过敏症状。本研究的目的是了解西替利嗪给药后的存活率和运动不协调（共济失调）副作用是否与给药时间有关。
总共240只10周龄的雄性瑞士小鼠，通过12小时光照（休息期）/12小时黑暗（活动期）同步饲养3周。在一天中的固定时间口服不同剂量的西替利嗪，以确定半致死剂量（TD(50)）和致死剂量（LD(50)），分别为55±0.35和750±0.40毫克/千克。在时辰毒理学研究中，在六个不同的昼夜节律阶段[光照开始后1、5、9、13、17、21小时（HALO）]给可比组的动物单次给予西替利嗪（DL(50)）。
存活率在统计学上具有显著的给药时间依赖性（χ(2)=16.73；P<0.001）。在光照开始后17小时给药的存活率为83.3%，而在光照开始后5小时给药的存活率仅为23.25%。余弦分析显示存活率存在统计学上显著的昼夜节律（周期约24小时）成分。当在光照开始后17小时和5小时分别给予西替利嗪时，共济失调发生率最低（20%）和最高（88%）。余弦分析显示共济失调存在统计学上显著的昼夜节律（周期约24小时）成分。
我们的结果表明，在小鼠黑暗（活动）期中间给予西替利嗪时安全性最佳，因为它会产生一些副作用：共济失调和体温过高。考虑西替利嗪的给药时间，可提高治疗效果并能更好地控制过敏性疾病。
