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

Background: The purpose of the present study was to measure the concentrati ons of cetirizine in the extracellular water compartment in intact human sk in and assess simultaneously inhibition of histamine-induced wheal and flar e reactions. Methods: Skin cetirizine levels were collected by the microdialysis techniq ue and analyzed by high-pressure liquid chromatography with mass spectromet ry 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 test s were performed with histamine 100 mg/ml. Results: Plasma cetirizine levels increased within 30 min to reach peak val ues of 315+/-10 and 786+/-45 ng/ml 90-120 min after administration of 10 an d 20 mg of cetirizine. This was followed by a slow decline. In the skin, di alysate cetirizine levels (nonprotein-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 c etirizine in the skin was 50-70% of corresponding plasma values. Both 10- a nd 20-mg doses of cetirizine inhibited wheal and flare reactions over 240 m in. The time vs concentration profile of cetirizine in skin dialysate paral leled the inhibition of skin reactions, but no significant correlations wer e found between individual cetirizine levels in skin or plasma with wheal a nd flare reactions. Conclusions: Cetirizine concentrations in the skin could be monitored by th e microdialysis technique. The results indicate no simple linear correlatio n between cetirizine skin levels and inhibition of skin reactions.