THE EFFECT OF CETIRIZINE AND LORATADINE ON CODEINE-INDUCED HISTAMINE-RELEASE IN HUMAN SKIN IN-VIVO ASSESSED BY CUTANEOUS MICRODIALYSIS

Objective and Design: To determine whether or not cetirizine and lorat adine inhibit codeine- induced histamine release in human skin in vivo , we conducted a placebo-controlled double-blind trial in which histam ine release was assessed by dermal microdiaysis. Subjects: A group of ten normal volunteers were studied, each subject visiting the laborato ry on three occasions with intervals of at least 2 weeks between visit s. Treatment: Cetirizine, loratadine (both 10 mg) or placebo was given orally 4 h before provocation of weal and flare responses in the skin by intradermal injection of 25 mu l of 3 or 10 mg/ml codeine 1 min fr om the centre of individual 216 mu m diameter microdialysis fibres ins erted in the dermis. Methods: Dialysate was collected at 2 min interva ls for 4 min before and 20 min after codeine injection and histamine a ssayed spectrofluorometrically. Weal and flare responses to codeine we re assessed in the opposite arm. Results: Histamine concentrations in the microdialysis fibre outflow with 3 and 10 mg/ml codeine were maxim al at 2 - 4 min when 910 +/- 156 and 1194 +/- 304 nM respectively were found in the placebo group. Cetirizine and loratadine did not modify either the kinetics or total histamine release while significantly (p < 0.01) inhibiting weal and flare responses. Conclusions: Neither ceti rizine nor loratadine inhibited codeine-induced histamine release or m odified the time course of its release in human skill in vivo when giv en in clinically used doses which are sufficient to significantly redu ce weal and Rare responses.