title: Hydroxyzine from topical phospholipid liposomal formulations: evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model.
abstract: Hydroxyzine, an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H(1)-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-alpha-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 < or =.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 < or =.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.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
authors.forename: Abeer A W
authors.initials: AA
authors.lastname: Elzainy
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Gu
authors.forename: F Estelle R
authors.initials: FE
authors.lastname: Simons
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006632:Histamine / Q000009:adverse effects; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006919:Hydroxyzine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008081:Liposomes / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011817:Rabbits; D011897:Random Allocation
chemical_list: D006634:Histamine H1 Antagonists; D008081:Liposomes; D010743:Phospholipids; D006919:Hydroxyzine; D006632:Histamine