title: 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.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Martin K
authors.initials: MK
authors.lastname: Church
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D003875:Drug Eruptions / Q000209:etiology* / Q000517:prevention & control; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use; D015230:Prostaglandin D2 / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D006634:Histamine H1 Antagonists; D010879:Piperazines; C487734:ceterizine hydrochloride; D017997:Leukotriene C4; C065679:icatibant; D006632:Histamine; D053802:Tryptases; D015230:Prostaglandin D2; D001920:Bradykinin