Dose-response relationship between objective measures of histamine-induced weals and dose of terfenadine

Terfenadine is a safe non-sedative H1-receptor antagonist. This study aimed to quantify the relative reduction in weal and flare area, thickness and erythema at 4, 8, 12 and 24 h following a single but variable oral dose of terfenadine compared with pre-treatment measurements, in order to compare the dose-effect relationship and time course of the different dosages. In a double-blind randomized cross-over study, 12 healthy volunteers were given 60, 120 or 240 mg of terfenadine or placebo. Twenty micrograms of histamine acid phosphate was then injected intradermally at 4, 8, 12 and 24 h. The weal and flare areas were measured by planimetry, the thickness of the weal by an A-scan pulsed ultrasound device and the redness of both the weal and flare by an erythema-meter. A definite dose-response relationship was demonstrated between the weal and flare areas and the three active treatments. For the weal area, there was a significant difference between 60 mg and 240 mg of terfenadine at 4 h (p less than 0.01), at 8 and 12 h (p less than 0.05). For the flare area there was a similar significant difference at 4 h (p less than 0.01) and at 8 h (p less than 0.05). A dose-response relationship was demonstrated between weal erythema and 120 mg or 240 mg and 60 mg of terfenadine (p less than 0.05). There was a correlation between the plasma levels of the major metabolite and the initial dose of terfenadine, demonstrating their expected proportionality. This metabolite was also demonstrated in tissue fluid.