Quantitation of H1-receptor antagonists in skin and serum

Cetirizine and hydroxyzine produce prompt, long-lasting peripheral H1-blockade in skin. We hypothesized that after oral administration of these H1-receptor antagonists, skin concentrations would be higher than serum concentrations and would correlate with peripheral H1 blockade.

In a randomized, double-blind, parallel-group study in 13 healthy subjects, skin biopsies, venipunctures, and epicutaneous tests with histamine were performed before ingestion of 10 mg cetirizine or 50 mg hydroxyzine and 1, 3, 6, 9, and 24 hours after administration. Subjects then took 10 mg cetirizine or 50 mg hydroxyzine at 21:00 hours for 6 consecutive days. All tests were repeated at 168 hours (steady state), 12 hours after the last dose.

Skin cetirizine concentrations were lower than serum ccetirizine concentrations from 1 to 9 hours but were higher at 24 hours and equivalent at 168 hours (steady state). Skin hydroxyzine concentrations were higher than serum hydroxyzine concentrations at all test times. After hydroxyzine dosing, cetirizine, the active metabolite of hydroxyzine arising in vivo, was found in skin and serum. Single doses of cetirizine or hydroxyzine produced highly significant suppression of wheals and flares from 3 to 24 hours inclusive, and this suppression was maintained at steady state.

Cetirizine and hydroxyzine enter the skin readily, and their sustained high concentrations in skin after single or multiple dosing may contribute to their well-known efficacy in symptomatic treatment of urticaria and other skin disorders in which histamine plays a role.