Cetirizine from topical phosphatidylcholine-hydrogenated liposomes: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model
Journal Title: The AAPS Journal - Year 2004, Vol 6, Issue 3
Abstract
Cetirizine, an effective, minimally sedating, second-generation H1-antihistamine is widely used orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of cetirizine from liposomes applied to the skin. Cetirizine was incorporated into small unilamellar vesicles (SUV) and multilamellar vesicles (MLV) prepared using L-α-phosphatidylcholine hydrogenated (HPC), and into Glaxal Base (GB) as the control. In a randomized, crossover study, each formulation, containing 10 mg of cetirizine, was applied to the depilated backs of 6 rabbits (3.08±0.05 kg). Histamine-induced wheal tests and blood sampling were performed before cetirizine application and at designated times for up to 24 hours afterwards. Compared with baseline, histamine-induced wheal formation was suppressed by cetirizine in SUV only at 24 hours, in MLV from 0.5 to 24 hours, and in GB from 0.5 to 8 hours (P<.05). Wheal suppression by cetirizine in SUV at 24 hours (91.7%±5.2%) and in MLV from 1 to 24 hours (93.8%±2.2% to 76.2%±6.5%) was greater than in GB (36.5%±7.4% to 60.6%±14.2%) from 1 to 24 hours (P<.05). Faster onset, as well as greater and more persistent suppression was obtained from cetirizine in MLV. Plasma cetirizine concentrations from MLV (area under the curve [AUC] of 221.2±42.3 ng.hr/mL) were lower than from GB (AUC of 248.3±34.6 ng.hr/mL). In this model, cetirizine from MLV had excellent topical H1-antihistamine activity, while systemic exposure was reduced, compared with cetirizine from GB.
Authors and Affiliations
Abeer A. W. Elzainy, Xiaochen Gu, F. Estelle R. Simons, Keith J. Simons
Keywords
Related Articles
- EP ID EP681924
- DOI 10.1208/aapsj060318
- Views 49
- Downloads 0
Determination of membrane protein glycation in diabetic tissue
Diabetes-associated hyperglycemia causes glycation of proteins at reactive amino groups, which can adversely affect protein function Although the effects of glycation on soluble proteins are well characterized, there is...
Nonclinical Dose Formulation: Out of Specification Investigations
Nonclinical safety studies are required to follow applicable Good Laboratory Practice (GLP) regulations. Nonclinical dose formulations are required to be analyzed to confirm the analyte concentration, homogeneity, and st...
Editorial: A New Series of Commentaries Entitled “Landmark Publications in the Pharmaceutical Sciences: The Backstory”
Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): Preparation and characterization
Low molecular weight protamine (LMWP) appears to be a promising solution for heparin neutralization without the protamine-associated catastrophic toxic effects. The feasibility of this hypothesis was proven previously by...
Compartmental Analysis and its Manifold Applications to Pharmacokinetics
The online version of this article (doi:10.1208/s12248-009-9160-x) contains supplementary material, which is available to authorized users.