Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)-antihistamines.

Abstract

Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H(1)-antihistamine. Intradermal injection of 100 μl of 100 μg/ml histamine and 10 mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1 × 10(-4) and 1 × 10(-5) M caused significant (P < 0.05) histamine release from isolated human cutaneous mast cells. In conclusion, icatibant induces histamine-mediated wheal and flare responses that may be reduced in severity by prophylactic administration of an H(1)-antihistamine.

• Authors: Marcus Maurer, Martin K Church
• Journal: Experimental dermatology (Exp Dermatol) Vol. 21 Issue 2 Pg. 154-5 (Feb 2012) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 22142018 (Publication Type: Clinical Trial, Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Adrenergic beta-Antagonists
• Histamine H1 Antagonists
• Piperazines
• ceterizine hydrochloride
• Leukotriene C4
• icatibant
• Histamine
• Tryptases
• Prostaglandin D2
• Bradykinin

Topics

• Adrenergic beta-Antagonists (administration & dosage, adverse effects, pharmacology)
• Bradykinin (administration & dosage, adverse effects, analogs & derivatives, pharmacology)
• Drug Eruptions (etiology, prevention & control)
• Histamine (metabolism, pharmacology)
• Histamine H1 Antagonists (therapeutic use)
• Histamine Release (drug effects)
• Humans
• Leukotriene C4 (metabolism)
• Mast Cells (drug effects, metabolism)
• Piperazines (therapeutic use)
• Prostaglandin D2 (metabolism)
• Tryptases (metabolism)