title: Potency and specificity of the pharmacological action of a new, antiasthmatic, topically administered soft steroid, etiprednol dicloacetate (BNP-166).
abstract: In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17alpha-dichloroacetoxy-11beta-hydroxyandrosta-1,4-diene-3-one-17beta-carboxylate), a new soft steroid, intended to use for the treatment of asthma, were investigated in an animal model of allergen sensitized and challenged Brown Norway rats using local treatment. The examinations involved the determination of the effect of the compound on the extent of allergen induced broncho-alveolar fluid and lung tissue eosinophilia, goblet cell hyperplasia and mucus production, perivascular edema formation, and airways hyperresponsiveness. The activity of etiprednol dicloacetate was compared with that of budesonide. Using in vitro methods, the soft character of etiprednol dicloacetate was investigated together with its capability to dissociate transrepressing and transactivating properties. We found that combining all the examined parameters etiprednol dicloacetate was at least equipotent with budesonide in the animal model, but in several investigated variables it surpassed the activity of budesonide. The effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of the serum, present in the assay, it was also strongly affected by the incubation time and decreased significantly when it was preincubated with human plasma. These features are characteristics of a soft drug that is quickly inactivated in the systemic circulation. In addition, it was revealed that while the transrepressing potential of etiprednol dicloacetate remained high, its transactivating activity was greatly reduced. These data indicate that the strong local effect of the compound will very likely be accompanied with a significantly reduced systemic activity predicting favorable selectivity in the pharmacological action of etiprednol dicloacetate.
authors.affiliation: Department of Immunopharmacology, IVAX Drug Research Institute, Budapest, Hungary. istvan.kurucz@idri.hu
authors.forename: István
authors.initials: I
authors.lastname: Kurucz
authors.forename: Szilveszter
authors.initials: S
authors.lastname: Tóth
authors.forename: Klára
authors.initials: K
authors.lastname: Németh
authors.forename: Katalin
authors.initials: K
authors.lastname: Török
authors.forename: Viola
authors.initials: V
authors.lastname: Csillik-Perczel
authors.forename: Agnes
authors.initials: A
authors.lastname: Pataki
authors.forename: Cecilia
authors.initials: C
authors.lastname: Salamon
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Nagy
authors.forename: József I
authors.initials: JI
authors.lastname: Székely
authors.forename: Katalin
authors.initials: K
authors.lastname: Horváth
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bodor
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000485:Allergens; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: D000305:Adrenal Cortex Hormones; D000485:Allergens; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; C450000:etiprednol dicloacetate; D019819:Budesonide