PHARMACOKINETICS OF EBROTIDINE IN HEALTHY-VOLUNTEERS - A SUMMARY

Several clinical pharmacokinetic studies of ebrotidine ethyl]amino]met hylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) administ ered by oral route in single and multiple doses to healthy Volunteers have been performed. Dosage levels were 150, 300, 400, 500, 600 and 80 0 mg. Plasma concentrations of unchanged ebrotidine and its major meta bolite, ebrotidine sulfoxide, excreted in the urine were determined. T he main pharmacokinetic parameters were calculated from the experiment al data. Absorption was relatively rapid (t(max) 2 h) and unrelated to dose. Drug behavior was considered as reasonably linear: C-max = 364- 1168 ng/ml and AUC(0-12h) = 1427-5997 ng . h/ml (doses from 150 mg to 800 mg). The mean values of terminal elimination half-life (t(1/2)beta ) ranged from 13.9 to 20.3 h (doses of 400, 600 and 800 mg). After mul tiple dosing there was no drug accumulation, and no significant change s in the mean values of the main pharmacokinetic parameters were obser ved. The steady state was reached from the second day of administratio n. 10-24% of the ebrotidine administered dose was excreted in urine ma inly as its major metabolite, ebrotidine sulfoxide, as well as unchang ed drug and other minor metabolites. These percentages were constant a nd independent of the dose administered.