Comparison of the Effects of Cetirizine and Ebastine on the Skin Response to Histamine Iontophoresis Monitored with Laser Doppler Flowmetry

Abstract

Background: The administration of histamine with iontophoresis is an alternative method to skin prick tests or intradermal injections. Skin reactions obtained with this method can be recorded with laser Doppler flowmetry (LDF) and previous studies with this method have shown histamine-induced laser Doppler changes in the wheal area. Objective: In order to compare the influence of two H₁ receptor antagonists (cetirizine 10 mg vs. ebastine 10 mg) on the skin vascular responses to histamine introduced by iontophoresis, we designed a double-blind, randomized, two-period crossover trial in which 18 volunteers were randomized. Methods: Before and 2, 5 and 7 h after drug administration, iontophoresis (30 s, 1.4 mA/cm²) of histamine 10% was performed and followed by (1) monitoring of skin vascular responses with LDF at the administration site and at 1 cm from it, and (2) wheal and flare area measurements. Results: 2, 5 and 7 h after intake of the antihistaminic drug, there were significant differences between both drugs. Concerning LDF recordings, we noted at the histamine administration site an increase in perfusion unit (PU) values which is an effect known to be in proportion to the degree of inhibition of wheal reaction, and at 1 cm distal to the histamine administration site, there was a decrease in PU values. These changes were more marked under cetirizine. A greater suppressive effect of cetirizine on the wheal and flare reaction was consistently observed at all time points during the study, demonstrating its superior efficacy. Conclusion: We conclude that (1) cetirizine demonstrated a stronger antihistaminic effect compared to ebastine at all time points; (2) iontophoresis appears to be an appropriate method to study specific microvascular changes at the delivery site of histamine and hence to detect the earliest changes occurring at the site of agonist-antagonist competition in the skin.

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study

“…In other studies levocetirizine reduced wheal and flare reaction to a greater extent than desloratadine, as well as other second generation antihistamines (Hindmarch et al, 2001;Grant et al, 2002;Denham et al, 2003;Purohit et al, 2003). A greater suppressive effect of cetirizine on the wheal and flare reaction compared to loratadine was demonstrated after histamine iontophoresis under physiological conditions differing from skin prick tests (Leroy et al, 1998). General trends for wheal and flare reaction obtained in our study were consistent with previous studies.…”

“…Laser Doppler flowmetry can be used to evaluate comparative effectiveness of various medical products, including H1-antihistamines (Rihoux et al, 1989;Hammarlund et al, 1990;Clough et al, 1998;Leroy et al, 1998;Clough et al, 2001). …”

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

“…Histamine has been delivered by iontophoresis to study the effect of antihistamine drugs (Leroy et al, 1998), to analyze neurogenic flare reactions (Bickel et al, 2002) and to assess the pharmacodynamics of histamine itself (Jones et al, 2009). Iontophoresis has also been used to study the effect of exercise (Rossi et al, 2005) and obesity (de Jongh et al, 2008) on the local microvascular responses to insulin as well as to investigate the role of calcitonin gene-related peptide in migraine (Edvinsson and Edvinsson, 2008;Rossi et al, 2007).…”

Efficacy Measurement of Topical Antihistamines

“…The amount of transmitted histamine could be varied by changing either the current strength or time of application according to Coulomb's law [33]. Leroy et al [1] used iontophoretic histamine application for the efficacy measurement of cetirizine versus ebastine. Weisshaar et al [18] induced pruritus by iontophoresis 15 min after topical application of several antihistamines and local analgesics in atopic patients.…”

“…Histamine exhibits a wide variety of both physiological and pathological functions in different tissues and cells [1]. The extracellular histamine action is mediated by binding to its specific cell surface receptors such as H 1 receptors in the skin and H 2 receptors in the parietal cells of the stomach.…”