Cetirizine from topical phosphatidylcholine liposomes: evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model.
This study was performed to assess the peripheral H(1)-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-alpha-phosphatidylcholine, and into Glaxal Base (GB), used as the control. In a randomized, cross-over study, each formulation, containing 10 mg of cetirizine, was applied to depilated areas on the backs of six 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 h. Compared with the baseline, histamine-induced wheal formation was suppressed by cetirizine in SUV and MLV from 0.5-24 h and by cetirizine in GB from 0.5-8 h, p</=0.05. Maximum wheal suppression by cetirizine in SUV and MLV ranged from 90.6%+/-4.9% to 89.0%+/-3.8% and 98.0%+/-1.3% to 94.0%+/-2.3%, respectively, from 6 to 8 h. The plasma cetirizine AUC of 201+/-24.2 ng.h/ml from SUV was lower than from PC-MLV, 334.6+/-65.1 ng.h/ml and from GB, 248.3+/-34.6 ng.h/ml. After 24 h, the percent of the cetirizine dose remaining on the backs of the rabbits from SUV was lower than from both MLV and GB, p</=0.05. In this model, cetirizine from both SUV and MLV had excellent topical H(1)-antihistaminic effects, while systemic exposure to cetirizine from SUV was reduced.
Elzainy
Abeer A W
AA
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
Gu
Xiaochen
X
Simons
F Estelle R
FE
Simons
Keith J
KJ
D000287:Administration, Topical; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D017332:Cetirizine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000517:prevention & control; D008081:Liposomes; D011817:Rabbits; D012869:Skin Absorption
D018926:Anti-Allergic Agents; D008081:Liposomes; D017332:Cetirizine