Purohit Ashok, Melac Michel, Pauli Gabrielle, Frossard Nelly
INSERM U425, Service de Pneumologie, Hôpitaux Universitaires, Strasbourg, France.
Br J Clin Pharmacol. 2003 Oct;56(4):388-94. doi: 10.1046/j.1365-2125.2003.01897.x.
Levocetirizine, the active enantiomer of cetirizine, and desloratadine, the active metabolite of loratadine, are two recently introduced anti-H1 agents. We set out to compare their antihistaminic activity in the skin for 24 h in a double-blind, randomized cross-over trial.
The skin reaction to histamine administered by prick tests (100 mg ml(-1)) was measured by the surface areas of weals and flares for 24 h [before treatment, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after a single dose of levocetirizine (5 mg), desloratadine (5 mg) or placebo] in 18 healthy volunteers (34.8 +/- 9.4 years; 14 women). The areas under the curves (AUC) of the weal and flare areas as a function of time were compared by ANOVA.
A highly significant overall treatment effect (P < 0.0001) was observed and both weals and flares were inhibited. The pairwise comparisons showed that the activity of levocetirizine and desloratadine was significantly superior to that of placebo (P < 0.0001), and the activity of levocetirizine was significantly superior to that of desloratadine (P < 0.0001). 'Total' weal inhibition (> or = 95%) occurred only with levocetirizine. Median values of maximal weal inhibition were 44.2% with placebo, 55.0% with desloratadine and 100% with levocetirizine. The time to maximal weal inhibition was 4 h (median value) for all three study drugs, but scattered over a wider range for desloratadine (3-24 h) than levocetirizine (2-4 h). With desloratadine, five of 18 (28%) subjects reached weal inhibition of at least 70% at between 3 and 10 h, whereas with levocetirizine all subjects [18/18 (100%)] reached this level of weal inhibition at between 1 and 3 h. The median duration of 70% weal inhibition was zero with placebo and desloratadine, and was 21.4 h with levocetirizine (P < 0.0001 between the three study drugs, and P < 0.0001 between the two active drugs). No uncommon adverse events were reported, and no subject withdrew from the study due to an adverse event.
This study shows that the activity of levocetirizine in suppressing skin reactivity to histamine was clearly superior to that of desloratadine for 24 h after a single dose. In addition, its activity was more consistent and lasted longer.
左西替利嗪是西替利嗪的活性对映体，地氯雷他定是氯雷他定的活性代谢产物，二者均为近期上市的抗H1药物。我们开展了一项双盲、随机交叉试验，比较二者在皮肤中24小时的抗组胺活性。
通过风团和红晕的表面积，测量18名健康志愿者（年龄34.8±9.4岁；14名女性）对皮内注射组胺（100mg/ml）的皮肤反应，测量时间为单剂量左西替利嗪（5mg）、地氯雷他定（5mg）或安慰剂给药前、给药后0.5、1、2、3、4、6、8、10、12及24小时。采用方差分析比较风团和红晕面积随时间变化的曲线下面积（AUC）。
观察到显著的总体治疗效果（P<0.0001），风团和红晕均受到抑制。两两比较显示，左西替利嗪和地氯雷他定的活性显著优于安慰剂（P<0.0001），且左西替利嗪的活性显著优于地氯雷他定（P<0.0001）。仅左西替利嗪出现了“完全”风团抑制（≥95%）。安慰剂组最大风团抑制的中位数为44.2%，地氯雷他定组为55.0%，左西替利嗪组为100%。三种研究药物达到最大风团抑制的时间均为4小时（中位数），但地氯雷他定的时间分布范围（3 - 24小时）比左西替利嗪（2 - 4小时）更广。使用地氯雷他定的18名受试者中有5名（28%）在3至10小时内风团抑制至少达到70%，而使用左西替利嗪的所有受试者[18/18（100%）]在1至3小时内达到了该风团抑制水平。安慰剂和地氯雷他定组70%风团抑制的中位数持续时间为零，左西替利嗪组为21.4小时（三种研究药物之间P<0.0001，两种活性药物之间P<0.0001）。未报告不常见的不良事件，也没有受试者因不良事件退出研究。
本研究表明，单剂量给药后24小时内，左西替利嗪抑制皮肤对组胺反应性的活性明显优于地氯雷他定。此外，其活性更稳定且持续时间更长。
