Dermal Objective Pharmacodynamic Profile of Cetirizine and Epinastine: Two Controlled, Randomised, Double‐blind, Crossover Studies

Abstract

SUMMARYTwo double‐blind clinical pharmacology studies were performed in healthy volunteers to compare the dermal pharmacodynamic profile of epinastine with cetirizine, a well‐documented anti‐H1 antagonist, after oral administration at the usual recommended dosage, i.e. 10 mg cetirizine and 20 mg epinastine (versus placebo). Histamine skin challenges (prick test) were evaluated before and at 1, 2, 4, 8 and 24 hr after drug intake by measuring the wheal and flare area (studies 1 and 2) along with laser Doppler monitoring of the microvascular responses (study 2). A decrease in wheal and flare areas was observed following intake of both drugs compared with placebo controls. With the notable exception of 1 hr post dose wheal values, which were consistently smaller after epinastine, cetirizine was superior to epinastine for both wheal and flare at all other times. At the prick test site, treatment with epinastine and cetirizine accentuated the increase in blood flow induced by histamine. This reflects the decrease of the whealing but there was no significant difference between the two active test compounds. At 1 cm from the prick test site, the administration of both active treatments inhibited the increase of blood flow, and cetirizine showed a more potent inhibitory effect from 8 hr post dose. This reflects the reduction of the flare induced after histamine‐receptor activation of the axon reflex. In conclusion, epinastine shows a rapidly greater (within 1 hr post dose on the wheal only) but vanishing effect than cetirizine. At all other time points, cetirizine was generally more effective than epinastine.