In vitro and in vivo anti-inflammatory properties and soft characteristics of
etiprednol dicloacetate (BNP-166) a new
steroid, which has been developed for the treatment of
asthma, were investigated in this study. The compound effectively decreased
cytokine production in
lipopolysaccharide stimulated lymphocytes and attenuated
lectin-induced proliferation of blood mononuclear cells in tissue culture. In an animal model of
allergen sensitized and challenged Brown Norway rats, using topical treatment,
etiprednol dicloacetate substantially attenuated the extent of
allergen induced bronchoalveolar fluid
eosinophilia. At every examined parameter its pharmacological effects were comparable to those of
budesonide. By means of in vitro
biological and analytical methods the soft character of
BNP-166 was also investigated. The anti-inflammatory effect of
etiprednol dicloacetate in vitro was shown to be the function of the quantity of serum components, present in the assay. This loss of activity was most likely the result of the fast metabolism of
etiprednol dicloacetate, which in the presence of sera could have been demonstrated by LC/MS/MS. Our data indicate that the significant local effect of the compound will very likely be accompanied with a drastically reduced systemic activity indicating an encouraging selectivity of the pharmacological action of
etiprednol dicloacetate.