Effect of olopatadine hydrochloride (KW-4679), an antiallergic drug, on peptide-leukotrienes release from human eosinophils

Olopatadine hydrochloride (KW-4679) has been shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. We have previously shown that KW-4679 inhibits A23187-induced peptideleukotrienes (p-LTs) release from guinea pig eosinophils (Int Arch Allergy Immunol 110：57-63,1996). In this study, we investigated the effect of KW-4679 on p-LTs release in human eosinophils purified from blood of healthy donors by negative selection using anti-CD16 antibody. When guinea pig eosinophils were stimulated with A23187 (1 μmol/L), the amounts of p-LTs and thromboxane (TX) B_2 released from eosinophils were 0.4 ng per 10^6 cells and 30 ng per 10^6 cells, respectively. In contrast, human eosinophils released p-LTs of 12 ng per 10^6 cells with 1 μmol/L A23187 stimulation, but TXB_2 release was not observed. KW-4679 concentration-dependently inhibited A23187-induced p-LTs release from human eosinophils, exhibiting IC_50 value of 4.5 μmol/L. Ketotifen also inhibited this reaction, IC_50 value was 39.4 μmol/L. These results suggest that KW-4679 show inhibitory effects on pLTs release in human eosinophils at lower concentration than ketotifen. The inhibitory effect on p-LTs release may contribute to the antiallergic efficacy of KW-4679.