组胺点刺皮肤试验的剂量—反应曲线下面积比较抗组胺药物的活性

Comparative Activity of Antihistamines on Area Under Dose-response Curve from Histamine-induced Wheal and Flare Responses in Human Skin

目的应用组胺点刺皮肤试验的剂量—反应曲线下面积(AUDRC)比较抗组胺药物(咪唑斯汀和氯雷他定)的抗组胺活性。方法90名健康志愿者及60例过敏性疾病患者,按随机、双盲的方法单次口服咪唑斯汀10mg,氯雷他定10mg或安慰剂1片。服药前及服药后2、4和24h分别进行组胺皮肤滴定试验,记录风团及红晕反应面积,计算AUDRC。结果健康志愿者和过敏患者在服药前及服药后2、4和24h的风团及红晕反应差异均无显著性。服药前,咪唑斯汀、氯雷他定和安慰剂3组的AUDRC2.7-54.3mmol/L差异无显著性。服药后,咪唑斯汀组和氯雷他定组的AUDRC2.7-54.3mmol/L均比服药前明显下降,且咪唑斯汀组的AUDRC2.7-54.3mmol/L下降幅度较大(P<0.01)。结论依据抗组胺药物对组胺点刺皮肤试验的抑制作用可建立药效动力学模型,AUDRC可作为比较抗组胺药物药效动力学活性的一个指标。

Objective To compare the activity of antihistamines by the index of area under dose-response curveAUDRCobtained from histamine-induced wheal and flare reactions. Methods Mizolastine 10 mg loratadine 10 mg and placebo were given to 90 healthy volunteers and 60 allergic patients in a double-blind and randomized manner. Histamine titration testshistamine concentrations 54.3 20.0 7.3 and 2.7 mmol/Lwere performed for each one before dosing and 2 4 and 24 hours after dosing. The reactivity was evaluated by histamine-induced wheal and flare areas. The AUDRC values of the wheal and flare areas as a function of the natural logarithm transformed histamine concentration were calculated for each subject and compared. Results There was no significant difference of the wheal and flare areas between health volunteers and allergic patients. The AUDRC2.7-54.3 mmol/L for wheal and flare of mizolastine was 115.7 23.4 7.7 49.8 and 902.1 40.9 2.6 46.9 lnmmol/L·mm2 at each timebefore dosing and 2 4 24 hours after dosingrespectively. Compared with loratadine116.2 80.2 49.7 71.9 and 957.6 495.3 153.5 205.9 lnmmol/L·mm2 mizolastine decreased AUDRC2.7-54.3 mmol/L significantlyP < 0.01. Conclusion Histamine-induced wheal and flare inhibition test is a reliable pharmacodynamic model for antihistamines and AUDRC may be an useful index to predict antihistamines pharmacodynamic activity.