Anti-inflammatory effect and soft properties of etiprednol dicloacetate (BNP-166), a new, anti-asthmatic steroid.
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.
Kurucz
I
I
Department of Immunopharmacology, IVAX Drug Research Institute, Budapest, Hungary.
Németh
K
K
Mészáros
S
S
Török
K
K
Nagy
Z
Z
Zubovics
Z
Z
Horváth
K
K
Bodor
N
N
D000305:Adrenal Cortex Hormones / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents; D001711:Biotransformation; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019819:Budesonide / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D037102:Lectins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D037102:Lectins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C450000:etiprednol dicloacetate; D019819:Budesonide