Simons F E, Silver N A, Gu X, Simons K J
Department of Pediatrics & Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Allergy Clin Immunol. 2001 Mar;107(3):526-30. doi: 10.1067/mai.2001.113080.
H1-receptor antagonists are widely used in the treatment of allergic skin disorders.
We sought to evaluate the extent of fexofenadine and diphenhydramine distribution into the skin concomitantly with their peripheral H1-receptor antagonist activity.
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.
Fexofenadine penetrated the skin to a significantly greater extent than diphenhydramine at 6, 9, 24, and 168 hours (P < or = .05). Maximum skin/plasma ratios of both the H1-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 < or = .05).
In disorders in which the presence and the effects of H1-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.
H1受体拮抗剂广泛用于治疗过敏性皮肤病。
我们试图评估非索非那定和苯海拉明在发挥外周H1受体拮抗活性的同时在皮肤中的分布程度。
在一项前瞻性、随机、双盲、平行组研究中，7名男性服用120mg非索非那定，7名服用50mg苯海拉明。给药前；首次给药后1、3、6、9和24小时；以及在第168小时（稳态），即第七次也是最后一次每日给药后12小时，采集血样和皮肤打孔活检标本，并进行1mg/mL磷酸组胺的皮内试验。
在6、9、24和168小时，非索非那定渗透到皮肤中的程度显著高于苯海拉明（P≤0.05）。两种H1拮抗剂的最大皮肤/血浆比值（非索非那定为41.3±7.8，苯海拉明为8.1±4.4）在24小时时获得。与苯海拉明相比，非索非那定在3、6和9小时对风团的抑制作用以及在3、6、9和168小时对红斑的抑制作用也显著更强（P≤0.05）。
在H1受体拮抗剂在皮肤中的存在和作用具有临床相关性的疾病中，我们的结果支持使用非索非那定，并表明有必要重新审视苯海拉明的作用。
