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INFLAMMATION AND IMMUNOPHARMACOLOGY

Potency and Specificity of the Pharmacological Action of a New, Antiasthmatic, Topically Administered Soft Steroid, Etiprednol Dicloacetate (BNP-166)

Department of Immunopharmacology (I.K., S.T., K.N., K.T., V.C.-P., Á.P., C.S., Z.N.), General Pharmacology (J.I.S.), Research and Development (K.H.) of IVAX Drug Research Institute, Budapest, Hungary; and IVAX Corporation (N.B.), Miami, Florida

In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17-dichloroacetoxy-11-hydroxyandrosta-1,4-diene-3-one-17-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.

Address correspondence to: István Kurucz, Department of Immunopharmacology, IVAX Drug Research Institute; Berlini u. 47-49, Budapest, Hungary H-1045. E-mail: istvan.kurucz{at}idri.hu

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