1147872-22-7

AM 103 has high bioavailability (64%), low clearance (2.9 mL/min/kg), low volume of distribution (0.41 L/kg), and a long i.v. half-life (5.2 h) in dogs. AM 103 (10 mg/kg q.i.d.) inhibits the increase in CysLTs and EPO by approximately 60%, and IL-5 levels are reduced to the concentrations obtained following saline treatment alone in mice^[1]. AM103 (1 mg/kg, p.o.) displays >50% inhibition for up to 6 h with a calculated EC₅₀ of appr 60 nM, in a rat ex vivo whole-blood calcium ionophore-induced LTB4 assay. AM 103 inhibits LTB4 and cysteinyl leukotriene (CysLT) production with ED₅₀ values of 0.8 and 1 mg/kg, respectively, when rat lung is challenged in vivo with calcium ionophore. In this model, the EC₅₀ derived from plasma AM103 is appr 330 nM for inhibition of both LTB4 and CysLT. In a model of chronic lung inflammation using ovalbumin-primed and challenged BALB/c mice, AM103 reduces the concentrations of eosinophil peroxidase, CysLTs, and interleukin-5 in the bronchoalveolar lavage fluid. Finally, AM 103 increases survival time in mice exposed to a lethal intravenous injection of platelet-activating factor^[2].