Measurement of interstitial cetirizine concentrations in human skin: correlation of drug levels with inhibition of histamine-induced skin responses.

Abstract

The purpose of the present study was to measure the concentrations of cetirizine in the extracellular water compartment in intact human skin and assess simultaneously inhibition of histamine-induced wheal and flare reactions. Skin cetirizine levels were collected by the microdialysis technique and analyzed by high-pressure liquid chromatography with mass spectrometry detection. Skin levels in 20 subjects were compared to plasma levels for 4 h after a single oral dose of 10 or 20 mg of cetirizine. Skin prick tests were performed with histamine 100 mg/ml. Plasma cetirizine levels increased within 30 min to reach peak values of 315+/-10 and 786+/-45 ng/ml 90-120 min after administration of 10 and 20 mg of cetirizine. This was followed by a slow decline. In the skin, dialysate cetirizine levels (non-protein-bound fraction only) peaked at 1.6+/-0.1 and 2.4+/-0.3 ng/ml at 120-180 min. In vivo recovery of cetirizine was 14.4+/-4.3%. It was estimated that the non-protein-bound concentration of cetirizine in the skin was 50-70% of corresponding plasma values. Both 10- and 20-mg doses of cetirizine inhibited wheal and flare reactions over 240 min. The time vs concentration profile of cetirizine in skin dialysate paralleled the inhibition of skin reactions, but no significant correlations were found between individual cetirizine levels in skin or plasma with wheal and flare reactions. Cetirizine concentrations in the skin could be monitored by the microdialysis technique. The results indicate no simple linear correlation between cetirizine skin levels and inhibition of skin reactions.