Acute effect of ketotifen on the dose-response curve of histamine and methacholine in asthma

Abstract

This study was designed to assess the acute effect of 1 mg of orally administered ketotifen on the dose-response curve to both histamine and methacholine, in 15 patients with bronchial asthma. From this curve we measured the concentration that produced a 20% fall in FEV 1 (PC 20) and reactivity, defined as the slope of the curve beyond the threshold dose. Results were analysed comparing the change in log PC 20 and in reactivity before and after a double-blind administration of ketotifen and placebo. Ketotifen, compared to placebo, significantly increased the histamine PC 20 ( P<0.001) and reduced reactivity ( P<0.001). After adjusting for starting FEV 1 the difference of effect between ketotifen and placebo was still significant, although to a lesser degree ( P<0.01). In contrast, ketotifen did not modify the methacholine dose-response curve. No significant changes were observed in FEV 1 after ketotifen. The results suggest that acute administration of ketotifen has a selective action on histamine-activated pathways of bronchoconstriction.