Effects of KW-4679, a New Orally Active Antiallergic Drug, on Antigen-Induced Bronchial Hyperresponsiveness, Airway Inflammation and Immediate and Late Asthmatic Responses in Guinea Pigs

Abstract

We investigated the effects of KW-4679, an antiallergic drug, on the development of bronchial hyperresponsiveness, airway inflammation and early and late asthmatic responses following aerosol antigen challenge in guinea pigs actively sensitized by the inhalation of aerosolized ovalbumin. Pretreatment with KW-4679 (10 mg/kg, p.o.) 1 h before antigen challenge prevented the development of bronchial hyperresponsiveness to inhaled methacholine. Examination of the bronchoalveolar lavage fluid 24 h after antigen challenge revealed the inhibitory effect of KW-4679 on the infiltration of eosinophils into the airway. Treatment with KW-4679 significantly inhibited both the immediate and late asthmatic responses. These results indicate that KW-4679 could be useful in the treatment of allergic diseases such as bronchial asthma.

Pharmacological, Pharmacokinetic and Clinical Properties of Olopatadine Hydrochloride, a New Antiallergic Drug

“…on the infiltration of eosinophils into the airway (12). Olopatadine at doses of 1 and 10 mg/ kg clearly inhibited the increase in R L at IAR and LAR (12). These results indicate that olopatadine could be useful in the treatment of bronchial asthma.…”

“…Examination of the bronchoalveolar lavage fluid 24 h after antigen challenge revealed the inhibitory effect of olopatadine (1, 3 and 10 mg/ kg, p.o.) on the infiltration of eosinophils into the airway (12). Olopatadine at doses of 1 and 10 mg/ kg clearly inhibited the increase in R L at IAR and LAR (12).…”

“…LAR is known to be accompanied by an increase in bronchial responsiveness to nonspecific stimulation and by the infiltration of inflammatory cells into the bronchial lumen. The effects of olopatadine on the development of bronchial hyperresponsiveness, airway inflammation and early and late asthmatic responses following aerosol antigen challenge in guinea pigs which were actively sensitized by the inhalation of aerosolized ovalbumin were investigated (12,13). As an index of bronchoconstriction in conscious guinea pigs, respiratory resistance (R L ), was automatically measured by a wholebody plethysmograph (14).…”

“…In the control group, the mean PC200 value was significantly reduced from 194.9 to 85.4 m g / mL after antigen challenge. When olopatadine was administered at 10 mg/ kg 1 h before antigen challenge, the mean PC200 values before and after antigen challenge were 148.1 and 182.9 m g / mL, respectively, indicating that olopatadine inhibits antigen-induced development of bronchial hyperresponsiveness (12). Kawasaki et al also investigated the effect of olopatadine on antigen-induced airway hyperresponsiveness to inhaled acetylcholine using R L and dynamic lung compliance (C dyn ) in actively sensitized guinea pigs under anesthesia.…”

Effect of KW-4679, an Orally Active Anti-allergic Drug, on Antigen-Induced Airway Hyperresponsiveness in Actively Sensitized Guinea Pigs

“…inhibited the production and/or release of TXB2 from leukocytes in bronchial alveolar lavage fluid of guinea pigs (Y. Sasaki, unpublished data). On the other hand, we recently demonstrated that KW-4679 inhibits the an tigen-induced development of AHR through the preven tion of eosinophil infiltration into guinea pig airways using a mild-symptoms experimental model that utilizes a single-antigen challenge with metyrapone (15). Conse quently, although the anti-asthmatic mechanism of KW 4679 has not been fully elucidated, it is considered that not only the inhibition of leukocyte infiltration but also the prevention of the action of chemical mediators (e.g., edema formation) such as TXA2, LTB4, PAF, tachykinins and especially histamine could contribute to the inhibi tory effect of KW-4679 on the development of AHR.…”