Clinical pharmacology of nedocromil sodium

Abstract

In attempts to define the clinical pharmacological activity of inhaled nedocromil sodium, various challenge systems, ranging from specific antigen challenge to provocation with chemical irritants such as sulphur dioxide, have been used. A single dose (4 mg) of nedocromil sodium taken before antigen challenge prevented both early and late asthmatic responses, whereas the same dose taken shortly after the early response delayed onset of the late reaction but did not affect its magnitude. Exercise-induced asthma was inhibited by pretreatment with nedocromil sodium, as were the bronchoconstrictor responses to hyperventilation of cold dry air and inhalation of ultrasonically nebulised distilled water ('fog'). Mast cells lying in the surface mucosa of the lung are thought to be less stable in asthmatic subjects and may be implicated in the mechanism of response to these 3 types of physical insult. However, in addition to the marked protective action on isolated mucosal mast cells which has been reported from preclinical studies, nedocromil sodium was also effective against bronchoconstriction induced by sulphur dioxide in hyper-responsive asthmatic and atopic subjects. The response to sulphur dioxide, in which axon reflexes are thought to be involved, is less likely to have an immunological mechanism and it is clear that in this type of situation the effect of nedocromil sodium can be more readily differentiated from that of sodium cromoglycate. The increased potency and wider scope of activity described for nedocromil sodium suggests a therapeutic advantage for this new compound in chronic inflammatory allergic lung disorders.