RT Journal Article
SR Electronic
T1 Potency and Specificity of the Pharmacological Action of a New, Antiasthmatic, Topically Administered Soft Steroid, Etiprednol Dicloacetate (BNP-166)
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 83
OP 92
DO 10.1124/jpet.103.053652
VO 307
IS 1
A1 István Kurucz
A1 Szilveszter Tóth
A1 Klára Németh
A1 Katalin Török
A1 Viola Csillik-Perczel
A1 Ágnes Pataki
A1 Cecilia Salamon
A1 Zoltán Nagy
A1 József I. Székely
A1 Katalin Horváth
A1 Nicholas Bodor
YR 2003
UL http://jpet.aspetjournals.org/content/307/1/83.abstract
AB In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17α-dichloroacetoxy-11β-hydroxyandrosta-1,4-diene-3-one-17β-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. The American Society for Pharmacology and Experimental Therapeutics