Pharmacokinetics of ebrotidine in rats and dogs

The pharmacokinetics of ebrotidine (N-[(E)-[[[2-[(diaminomethylene)amino] -4-thiazolyl]methyl]thio]ethyl] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) was studied in the rat and dog. After oral (agar suspension) and intravenous administration at 10 mg/kg to rats, ebrotidine was rapidly absorbed. Cmax values averaged 0.498 microgram/ml attained at tmax = 30 min. Distribution was fitted to a two-compartmental model with t1/2 beta = 1 h (i.v.). Clearance (Cl) was 29 ml/min.kg and volume of distribution (Vdss) was 1852 ml/kg. Absolute bioavailability was 22% of the dose administered. After oral (the same tablet formulation as that used for clinical trials) and intravenous administration at 150 mg and 25 mg, respectively, to dogs, absorption of ebrotidine was relatively rapid. Cmax values averaged 2,170 micrograms/ml attained at tmax = 2 h. Distribution was fitted to a two-compartmental model with t1/2 beta = 2.8 h (i.v.). Clearance (Cl) was 600 ml/h.kg and volume of distribution (Vdss) was 1000 ml/kg. Absolute bioavailability, which is variable in this type of drugs, ranges from 29% to 64% of the dose administered.