Inhibition of the cutaneous response to histamine by H1-blocking agents. Quantitative evaluation of microvascular changes in the skin after histamine challenge and a comparison of the effects of a single intake of cetirizine and terfenadine.

A controlled, randomized, double-blind, cross-over study was performed in 10 healthy volunteers in order to compare changes of cutaneous blood flow values (CBFV, laser Doppler flowmetry, Periflux, Perimed, S) in histamine-challenged skin before and after administration of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. The overall pattern of the basal cutaneous wheal and flare response to the agonists (histamine: aqueous solution: Hsol, or Phazet: Hprick) and control saline solution, showed the expected range of clinical effects, i.e. Hsol greater than Hprick greater than saline. Similarly, the increase of CBFV on the flare area was higher around the histamine injections as compared with saline. Surprisingly, CBFV was decreased at the site of Hsol and Hprick injections as compared with the levels recorded at the control injections. The following changes were noted after intake of H1-blocking agents. (1) There was a reduction of the areas of wheal and flare at all injection sites after administration of the H1 blockers, this reduction being consistently greater under cetirizine than terfenadine. (2) CBFV, measured 1 cm from the site of Hsol injection (i.e., within the area of normal flare response), was decreased only with cetirizine. In the smaller flare area induced by Hprick, CBFV was equally suppressed by both drugs. (3) At the site of agonist injection, along with a reduction of the size of the wheal, we observed significant increases in CBFV after drug intake. Under these experimental conditions, this quantitative pharmacologic in vivo assay of agonist-antagonist interactions suggests that after initial administration of normally prescribed doses, cetirizine may possess more anti-H1 activity than terfenadine.