Skin concentrations of H1-receptor antagonists

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.