Antihistaminic activity and side effect profile of epinastine and terfenadine in healthy volunteers.

New H1-receptor antagonists are assessed not only for their H1 antihistaminic activity but also for their central nervous system (CNS) side effects. Fifteen healthy subjects received a once daily dose of 5 mg, 10 mg or 20 mg of epinastine, or a twice daily dose of 60 mg of terfenadine or placebo in a randomized double-blind (double-dummy) crossover study. The response to histamine-induced skin wheals was compared. CNS effects were evaluated by a multiple reaction time task, a finger tapping test and a self-rating scale (Bf-S von Zerssen) to assess mood state. Epinastine attenuated the wheal size in response to histamine in a dose-dependent manner. In addition, all epinastine dosages had a distinctly faster onset of action than terfenadine. All active treatments (5 mg, 10 mg, 20 mg epinastine and 60 mg terfenadine) attained their maximum effects 4 h after administration. At this time point and also 12 h after administration, 20 mg of epinastine were significantly more effective than 60 mg of terfenadine. Single 10 mg and 20 mg doses of epinastine were as effective as terfenadine given twice daily, and significantly more effective than placebo 24 h after drug administration (i.e. 12 h after the second dose of terfenadine). The psychometric tests for CNS effects did not reveal any difference among epinastine, terfenadine and placebo. In conclusion, epinastine is one of the most effective peripherally acting H1 antagonist which lacks significant CNS side effects and is suitable as a once daily dosage regimen.