布那司特

Bunaprolast (U-66,858) undergoes deacetylation to an initial metabolite with similar pharmacological potency. The inhibitory effects of the semi-quinone Bunaprolast and its metabolite U-68,244 on the ionophore-induced formation of leukotriene B4 (LTB4) are examined in human whole blood (WB). Preincubation of Bunaprolast and U-68,244 for 1 min prior to challenge of blood with calcium ionophore A23187 results in IC ₅₀ s of 1080±644 and 820±442 nM, respectively. After 60 min preincubation, IC ₅₀ s are 250±85 and 270±79 nM. The activity of the lipoxygenase inhibitor AA-861 in this system is similar to that of Bunaprolast, while vitamin K and the sulphate conjugate of Bunaprolast show significant inhibition of LTB4 release only at micromolar concentrations. Bunaprolast exhibits significant inhibition of thromboxane A2 release (p<0.02) in a comparative study with the known cyclooxygenase (CO) inhibitor Flurbiprofen.

The IgE-mediated hypersensitivity to Ascaris antigen in reactor rhesus primates is used to assess the pharmacologic profile of Bunaprolast (U-66,858). When Bunaprolast is given by the oral route, it shows dose-related inhibition of resistance (RL) and compliance (Cdyn) changes. When Bunaprolast is given by the aerosol route, it shows dose independent inhibition. In 15 animals, aerosols (52±32 to 53±10% for RL, p=0.05 and 45±19 to 28±19% Cdyn inhibitions, p=0.05) for 5.0-0.1% aerosol. By the oral route, inhibition is seen at 1-4 h following administration. In 5 animals, oral doses of 10 and 5 mg/kg inhibit (RL by 98±2 to 78±1.5%, p=0.01 and Cdyn by 75±17 to 60.9±9.1%, p=0.05) by 10 and 5 mg/kg Bunaprolast, respectively.