Hydroxyzine an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-α-phosphatidylcholine (PC), small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) containing hydroxyzine were prepared. Hydroxyzine in Glaxal Base (GB) was used as the control. Using a randomized, crossover design, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 rabbits (3.08 ± 0.05 kg). Histamine-induced wheal tests and blood sampling were performed at designated time intervals up to 24 hours. Compared with baseline, hydroxyzine from all formulations significantly suppressed histamine-induced wheal formation by 75% to 95% for up to 24 hours. Mean maximum suppression, 85% to 94%, occurred from 2 to 6 hours, with no differences among the formulations. The areas of plasma hydroxyzine concentration versus time area under the curve (AUCs) from PC-SUV and PC-MLV, 80.1 ± 20.8 and 78.4 ± 33.9 ng/mL/h, respectively, were lower than that from GB, 492 ± 141 ng/mL/h (P = .05) over 24 hours. Plasma concentrations of cetirizine arising in-vivo as the active metabolite of hydroxyzine, from PC-SUV, PC-MLV, and GB, were similar with AUCs of 765 ± 50, 1035 ± 202, and 957 ± 227 ng/mL/h, respectively (P = .05). Only 0.02% to 0.06% of the initial hydroxyzine dose remained on the skin after 24 hours. In this model, hydroxyzine from SUV and MLV had excellent topical H1-antihistaminic activity, and minimal systemic exposure occurred. Cetirizine formed in-vivo contributed to some of H1-antihistaminic activity.
CITATION STYLE
Elzainy, A. A. W., Gu, X., Simons, F. E. R., & Simons, K. J. (2003). Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model. AAPS PharmSci, 5(4). https://doi.org/10.1208/ps050428
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