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

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 FEV1 (PC20) and reactivity, defined as the slope of the curve beyond the threshold dose. Results were analysed comparing the change in log PC20 and in reactivity before and after a double-blind administration of ketotifen and placebo. Ketotifen, compared to placebo, significantly increased the histamine PC20 (P less than 0.001) and reduced reactivity (P less than 0.001). After adjusting for starting FEV1 the difference of effect between ketotifen and placebo was still significant, although to a lesser degree (P less than 0.01). In contrast, ketotifen did not modify the methacholine dose-response curve. No significant changes were observed in FEV1 after ketotifen. The results suggest that acute administration of ketotifen has a selective action on histamine-activated pathways of bronchoconstriction.