The Japanese perspective: effects of terfenadine in bronchial asthma: in vitro and in vivo research.

The development of newer, more potent, nonsedating H1-receptor antagonists has led to a reappraisal of the potential of this class of drugs in the treatment of asthma. Studies conducted in Japan have examined the pharmacologic profile and clinical efficacy of one of these newer agents, terfenadine. In vitro, terfenadine inhibited the release of histamine from rat peritoneal mast cells and guinea pig lung tissue and conjunctiva in response to such stimuli as compound 48/80, concanavalin A, substance P, A-23187, and the partial peptide of eosinophil major basic protein. Ketotifen had similar, though less potent, antiallergic activity in these models. Mechanisms that appear to be involved in the mediation of this inhibitory effect include the prevention of intracellular calcium ion release and calcium uptake, the inhibition of protein kinase C translocation, and the activation of adenylate cyclase and the resulting accumulation of cyclic AMP (cAMP). A multicenter, double-blind, controlled clinical trial compared the efficacy of ketotifen, 2 mg bid, with that of terfenadine, given at doses of 120 or 240 mg bid (two or four times the US recommended dose, respectively) in the treatment of mild to moderate atopic and mixed-type asthma in adults. Physician assessment of overall improvement and patient evaluation of response were somewhat better with terfenadine, particularly the 120-mg bid dose. As in other comparative studies of these two drugs, terfenadine produced less drowsiness than ketotifen.