PHARMACOKINETICS OF EBROTIDINE IN RATS AND DOGS

The pharmacokinetics of ebrotidine ethyl]amino]methylene]-4-bromo-benz enesulfonamide, CAS 100981-43-9, FI-3542) was studied in the rat and d og. After oral (agar suspension) and intravenous administration at 10 mg/kg to rats, ebrotidine was rapidly absorbed. C-max values averaged 0.498 mu g/ml attained at t(max) = 30 min. Distribution was fitted to a two-compartmental model with t(1/2 beta) = 1 h (i.v.). Clearance (Cl ) was 29 ml/min.kg and Volume of distribution (Vd(ss)) was 1852 ml/kg. Absolute bioavailability was 22 % of the dose administered. After ora l (the same tablet formulation as that used for clinical trials) and i ntravenous administration at 150 mg and 25 mg, respectively, to dogs, absorption of ebrotidine was relatively rapid. C-max values averaged 2 .170 mu g/ml attained at t(max) = 2 h. Distribution was fitted to a tw o-compartmental model with t(1/2 beta) = 2.8 h (i.v.). Clearance (Cl) was 600 ml/h.kg and volume of distribution (Vd(ss)) was 1000 ml/kg. Ab solute bioavailability, which is variable in this type of drugs, range s from 29 % to 64 % of the dose administered.