Ketotifen in atopic asthma and exercise-induced asthma.

Abstract

The efficacy of ketotifen, a tricyclic benzocycloheptathiophene derivative, was assessed in an outpatient clinical trial and in a group of 12 asthmatic subjects with exerciseinduced asthma. Subjects in the outpatient trial had mild asthma and consisted of two groups: a group of 24 atopic asthmatics with at least one positive skin test reaction and with an associated history of bronchial reactivity to at least one allergen; and a group of eight asthmatics with one or more positive skin prick tests but no bronchial reactivity to an allergen. Both groups took four weeks medication of ketotifen 1 mg bd and placebo in a randomised double-blind crossover study. There was no difference between ketotifen and placebo for any measurement made during the study and consequently no evidence of drug efficacy. The exercise study followed a standardised protocol and each subject took in random double-blind order, placebo, 1 mg, 2 mg, and 4 mg ketotifen two hours before exercise. There was no difference in the mean decreases in lung function from pre-exercise baseline values after three doses of ketotifen than with placebo. Drug levels suggested ketotifen was well absorbed. It would appear that if given for a period of only four weeks ketotifen has no beneficial effects in the management of mild asthma, and that a single dose before exercise does not modify exercise-induced asthma.Ketotifen, an orally active tricyclic benzocycloheptathiophene derivative, has several properties suggesting it might be useful in the management of asthma.' 2 It inhibits passive cutaneous anaphylaxis and has a mast cell stabilising effect. It is also a potent antihistamine specific for Hi receptors with little anticholinergic activity and it raises intracellular cyclic-AMP levels by inhibiting phosphodiesterase.' 2 Ketotifen has been shown to be effective in preventing histamine-induced bronchospasm,34 aspirin and tartrazine-induced asthma,5 and as effective as disodium cromoglycate in controlling allergen-induced bronchospasm.3 Proof of its efficacy in preventing exercise-induced bronchospasm is confined to a single comparative study with cromoglycate which showed good protection in eight of 11 subjects.3 Controlled trials assessing the value of ketotifen as prophylaxis for asthma in outpatients have given inconclusive results. It has been shown to be as effective as disodium

Wheat-dependent, Exercise-induced Anaphylaxis: A Successful Case of Prevention with Ketotifen

“…Antihistamines may be helpful in the treatment of FDEIA and may be useful in the prevention of urticaria or angioedema 5 . Ketotifen is an orally active tricyclic benzocyclo-heptathiophene derivative and thus may be a useful medication in the treatment and prevention of allergic responses 16 . Ketotifen is a potent H1 receptor antagonist which has properties of mast cell stabilization and anti-inflammatory capabilities.…”

“…Ketotifen also has other anti-inflammatory properties, which include reduced eosinophilic chemotaxis in eosinophilia and diminished production of eotaxin and expression of CD29 in epithelial cells 17 . Previous reports have not reached a consensus on the efficacy of ketotifen in preventing EIA [16][17][18] . In the case reported herein, however, we observed that 1 mg of ketotifen 2 hours before wheat ingestion prevented FDEIA.…”

Current Concepts of Exercise‐Induced Asthma

“…These include oxatomide (78), RS7640 a xanthone (82), doxantrazole (67) and FPL57787 an oral chromone (88). Oral ketotifen does not inhibit EIA (6,66).…”

Does regular treatment with ketotifen inhibit bronchoconstriction induced by isocapnic hyperventilation?

“…Several studies have demonstrated inhibition by ketotifen ofhistamineinduced (Craps et al, 1978) and allergen-induced (Craps et al, 1978;Palmen, 1983) bronchoconstriction, but reports of its efficacy in exerciseinduced asthma (EIA) are conflicting (Craps et al, 1978;Dorward & Patel, 1982;Petheram et al, 1981;Kennedy etal., 1980;Lilja etal., 1983). Most of these studies were performed after 3 weeks or less of treatment with ketotifen and it has been suggested that the maximum effect may not be achieved until 5 weeks after treatment has been commenced (Gobel, 1978).…”