Lack of subsensitivity to terfenadine during long-term terfenadine treatment

Eleven healthy male volunteers ingested terfenadine, 60 mg, every 12 hours for 56 days. Compliance was monitored strictly throughout the study. Before the first terfenadine dose on day 0, and 12 hours after the evening terfenadine dose every seventh day and on randomly selected "unscheduled" days, wheal-and-flare areas were measured after intradermal injections of 0.01 ml of histamine phosphate (1.0 mg/ml and 0.1 mg/ml). On days 0, 28, and 56, six volunteers had skin tests hourly for 12 hours after the morning terfenadine dose. On all study days, serum terfenadine metabolite I concentrations were measured each time histamine skin tests were performed. On days 7, 14, 21, 28, 35, 42, 49, and 56, the mean areas of the histamine-induced wheals did not differ significantly from each other but were significantly decreased compared to the mean wheal area on day 0 (p less than 0.01). On these days, the mean areas of the histamine-induced flares also did not differ significantly from each other but remained significantly suppressed compared to the mean flare areas on day 0 (p less than 0.01). Wheal-and-flare suppression was noted in all unscheduled histamine skin tests performed 12 hours after the evening terfenadine dose. In the subgroup of volunteers who had hourly tests, on day 0, the mean wheal-and-flare areas were significantly suppressed from 2 to 12 hours after the dose, with maximal wheal suppression occurring at 5 hours (p less than 0.05) and maximal flare suppression occurring from 3 to 9 hours (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)