Horak Friedrich, Zieglmayer Petra U, Zieglmayer R, Kavina A, Lemell P
Vienna General Hospital (AKH), Department of Otorhinolaryngology, Vienna, Austria.
Br J Clin Pharmacol. 2005 Jul;60(1):24-31. doi: 10.1111/j.1365-2125.2005.02377.x.
To compare the onset and duration of action of the new antihistamine levocetirizine with that of the second-generation antihistamine fexofenadine using the Vienna Challenge Chamber (VCC). The latter is an environment where subjects can be exposed to specific aeroallergens in controlled and reproducible conditions allowing for precise comparisons of anti-allergic drugs.
Ninety-four subjects received a single dose of levocetirizine 5 mg, fexofenadine 120 mg or placebo in a random order using a three-way cross-over design. On day 1, subjects were exposed to grass pollens (1500 grains/m(3)) in the VCC over a period of 4 h. Treatment was given 2 h after the start of challenge. On day 2, 22 h after drug intake, subjects were again exposed to pollens for 6 h. Specified symptoms were assessed by the subjects every 15 min using 5-point scales. The main efficacy parameter was the change from baseline in the Major Symptom Complex Score (MSCS = sum of rhinorrhea, sneezing, itchy nose and eyes).
Baseline characteristics, including symptoms scores, were similar in the three study groups. During the first 2 h after drug intake both antihistamines achieved clinically relevant and significant (P < 0.001) improvements in symptom scores. Twenty-two to 24 h after drug intake, mean (SEM) MSCS reductions were: 1.9 (0.3) after placebo (baseline of 9.7), 3.8 (0.3) after fexofenadine (baseline of 9.9), and 5.1 (0.3) after levocetirizine (baseline of 9.8). Levocetirizine was significantly (P < 0.001) more effective than fexofenadine with a score difference of 1.3 (95% CI 0.7, 1.9). This was maintained until the end of the study (up to 28 h).
A rapid onset of action in alleviating seasonal allergic rhinitis (SAR) symptoms of subjects exposed to grass pollens in the VCC was observed after levocetirizine and fexofenadine. Levocetirizine was more effective than fexofenadine at and later than 22 h after drug intake, an indication of the longer-duration of action of levocetirizine.
使用维也纳激发试验箱(VCC)比较新型抗组胺药左西替利嗪与第二代抗组胺药非索非那定的起效时间和作用持续时间。后者是一个能让受试者在可控且可重复的条件下接触特定空气变应原的环境,便于精确比较抗过敏药物。
94名受试者采用三向交叉设计,随机依次接受单剂量5毫克左西替利嗪、120毫克非索非那定或安慰剂。第1天,受试者在VCC中暴露于草花粉(1500粒/立方米)4小时。激发开始2小时后给药。第2天,在服药22小时后,受试者再次暴露于花粉6小时。受试者每15分钟使用5分制量表评估特定症状。主要疗效参数是主要症状综合评分(MSCS = 流涕、打喷嚏、鼻痒和眼痒评分之和)相对于基线的变化。
三个研究组的基线特征,包括症状评分,相似。在服药后的前2小时,两种抗组胺药均使症状评分取得了具有临床意义的显著改善(P < 0.001)。服药后22至24小时,平均(SEM)MSCS降低值分别为:安慰剂组为1.9(0.3)(基线为9.7),非索非那定组为3.8(0.3)(基线为9.9),左西替利嗪组为5.1(0.3)(基线为9.8)。左西替利嗪比非索非那定显著更有效(P < 0.001),评分差异为1.3(95% CI 0.7,1.9)。这种差异一直维持到研究结束(长达28小时)。
观察到左西替利嗪和非索非那定在缓解VCC中暴露于草花粉的受试者季节性变应性鼻炎(SAR)症状方面起效迅速。左西替利嗪在服药22小时及之后比非索非那定更有效,表明左西替利嗪的作用持续时间更长。