Skin concentrations of H1-receptor antagonists

被引:45
作者
Simons, FER
Silver, NA
Gu, XC
Simons, KJ
机构
[1] Univ Manitoba, Fac Pharm, Winnipeg, MB, Canada
[2] Univ Manitoba, Fac Med, Dept Pediat & Child Hlth, Winnipeg, MB, Canada
关键词
H-1-receptor antagonist; antihistamine; fexofenadine; diphenhydramine; skin punch biopsy; wheat; flare; histamine blockade; adults; urticaria;
D O I
10.1067/mai.2001.113080
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: H-1-receptor antagonists are widely used in the treatment of allergic skin disorders. Objective: We sought to evaluate the extent of fexofenadine and diphenhydramine distribution into the skin concomitantly with their peripheral H-1-receptor antagonist activity. Methods: In a prospective, randomized, double-blind, parallel-group study, 7 men received 120 mg of fexofenadine, and 7 received 50 mg of diphenhydramine. Before dosing; at 1, 3, 6, 9, and 24 hours after the first dose; and at 168 hours (steady-state), 12 hours after the seventh and last daily dose, blood samples and skin punch biopsy specimens were obtained, and epicutaneous tests with histamine phosphate, 1 mg/mL, were performed. Results: Fexofenadine penetrated the skin to a significantly greater extent than diphenhydramine at 6, 9, 24, and 168 hours (P less than or equal to .05). Maximum skin/plasma ratios of both the H-1-antagonists (41.3 +/- 7.8 for fexofenadine and 8.1 +/- 4.4 for diphenhydramine) were obtained at 24 hours. Fexofenadine also produced significantly greater suppression of wheals at 3, 6, and 9 hours and of flares at 3, 6, 9, and 168 hours compared with diphenhydramine (P less than or equal to .05). Conclusion: In disorders in which the presence and the effects of H-1-receptor antagonists in the skin are clinically relevant, our results support the use of fexofenadine and indicate the need to re-examine the role of diphenhydramine.
引用
收藏
页码:526 / 530
页数:5
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