Epinastine: An update of its pharmacology, metabolism, clinical efficacy and tolerability in the treatment of allergic diseases.

Abstract

Epinastine is a potent antiallergic agent that has not only antihistaminic (H(1)) properties but also provides antileukotriene, anti-PAF and antibradykinin activities, which are associated with its antiallergic actions. Moreover, epinastine is very effective in inhibiting the release of chemical mediators from mast cells exposed to antigen. In addition, IL-8 release from eosinophils was inhibited by epinastine posttranscriptionally. Chemotatic movement of eosinophils was also blocked by epinastine. The increase in EEG power spectrum at low frequency region detected at frontal cortex is associated with drowsiness. No such change was induced by epinastine, while a marked increase was observed after ketotifen. In agreement with this, when the amount of H(1) blockers that penetrated through the BBB into the brain was estimated by means of PET, it was apparent that epinastine hardly penetrated the BBB. With regard to the current-voltage relationship of HERG currents, epinastine did not affect I(Kr), while a marked inhibition was seen after terfenadine or astemizole. These results indicated that epinastine does not suppress delayed rectifier potassium current of the heart and, consequently, no cardiotoxic action of epinastine was postulated. In man, epinastine is readily absorbed after oral administration and no significant change in pharmacokinetics was found during chronic administration. In teratological studies in rats, malformation and variation were not observed even at high doses of epinastine. In the clinical application of epinastine, it was shown that this drug is remarkably effective in the treatment of various dermatological diseases, such as chronic urticaria, psoriasis vulgaris and other pruritic dermatoses. Moreover, epinastine provides excellent clinical efficacy in the treatment of allergic rhinitis. Although efficacy of H(1) blockers in bronchial asthma is somewhat doubtful, the overall improvement rate in asthmatic patients was significantly higher in epinastine-treated patients (53.7%) compared to those treated with ketotifen (25%).