Reference

Pharmacokinetics of ebrotidine in healthy volunteers

Pharmacokinetics of ebrotidine in healthy volunteers. Albet, Carlos; Perez, Jose A.; Rozman, Elena; Marquez, Miguel; Herrero, Eduardo; Ortiz, Jose A. (Centro Investigacion Farmaceutica Grupo Ferrer, Barcelona E-08028, Spain). Arzneimittel-Forschung, 47(4a), 535-539 (English) 1997 Cantor. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Several clin. pharmacokinetic studies of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]a mino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) administered by oral route in single and multiple doses to healthy volunteers have been performed. Dosage levels were 150, 300, 400, 500, 600 and 800 mg. Plasma concns. of unchanged ebrotidine and its major metabolite, ebrotidine sulfoxide, excreted in the urine were detd. The main pharmacokinetic parameters were calcd. from the exptl. data. Absorption was relatively rapid (tmax = 2 h) and unrelated to dose. Drug behavior was considered as reasonably linear: Cmax = 364-1168 ng/mL and AUC0-12 h = 1427-5997 ng × h/mL (doses from 150 mg to 800 mg). The mean values of terminal elimination half-life (t1/2b) ranged from 13.9 to 20.3 h (doses of 400, 600 and 800 mg). After multiple dosing there was no drug accumulation, and no significant changes in the mean values of the main pharmacokinetic parameters were obsd. The steady state was reached from the second day of administration. 10-24% Of the ebrotidine administered dose was excreted in urine mainly as its major metabolite, ebrotidine sulfoxide, as well as unchanged drug and other minor metabolites. These percentages were const. and independent of the dose administered.

Pharmacokinetic study of ebrotidine administered in multiple doses to healthy volunteers for 4 days

Pharmacokinetic study of ebrotidine administered in multiple doses to healthy volunteers for 4 days. Frias, Jesus; Esteban, Carmen; Carcas, Antonio J.; Sanchez-Garcia, Pedro; Albet, Carlos; Torres, Jesus; Marquez, Miguel; Ortiz, Jose A. ( Facultad Medicina, Madrid Autonomous University, Madrid E-28029, Spain). Arzneimittel-Forschung, 47(4a), 5531-5534 (English) 1997 Cantor. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]a mino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542), a new H2-receptor antagonist with gastroprotective activity, was assessed and its main pharmacokinetic parameters were detd. in order to establish the dose linearity after the repeated administration of three different dose levels. The study was carried out in a group of 8 healthy volunteers of either sex, aged between 20 to 29 yr. Oral doses of ebrotidine were administered in a randomized, single-blind design. Volunteers remained in the Unit for two days at each of the three study phases with washout intervals of 2 wk and received seven doses of ebrotidine (150, 300 and 500 mg b.i.d). Pharmacol. evaluation included vital signs, lab. tests, adverse events and blood and urine samplings for pharmacokinetic anal. Ebrotidine was detd. by high performance liq. chromatog. (HPLC) with UV detection. The results showed a good tolerability of ebrotidine after the administration of seven doses for 4 days, with no changes in the vital signs or lab. parameters. No clin. significant dose-related adverse events were reported during the study. The absorption of ebrotidine was relatively rapid (tmax u 2 h) and linear within the dose range from 150 to 500 mg. Drug biotransformation was linear with doses tested, and no metabolic satn. occurred. The terminal elimination half-life of ebrotidine was between 7 and 11 h or even longer. There was no accumulation of ebrotidine and the steady state was reached, regardless of the dose administered, within the first 24-48 h.