Tolerability and pharmacokinetics of ebrotidine in healthy subjects given single and repeated oral doses.
The tolerability and safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) and its basic pharmacokinetic parameters were determined after its oral administration to healthy volunteers. Sixteen subjects were selected to participate in two different studies: an increasing single dose study to determine the maximal tolerated dose (from 25 to 1600 mg), and a multiple dose study (stepped doses from 400 to 1600 mg daily for 12 days). The results of the studies showed that ebrotidine has a good tolerability. Vital signs and laboratory tests were not influenced by the study treatment. No clinically relevant adverse effects were reported during the investigation. Ebrotidine reached peak plasma concentrations 2-3 h after oral administration. Its elimination half-life ranged from 9 to 14 h. In conclusion, ebrotidine was well tolerated after administration of oral single doses of up to 1600 mg, and after repeated administration of up to 800 mg/12 h for 12 days.
Farré
M
M
Department of Pharmacology and Toxicology, Institut Municipal d'Investigació Mèdica, Universitat Autònoma de Barcelona, Spain.
Roset
P N
PN
Badenas
J M
JM
Ugena
B
B
Márquez
M
M
Albet
C
C
Herrero
E
E
Ortiz
J A
JA
D000284:Administration, Oral; D000328:Adult; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D013844:Thiazoles; C075156:ebrotidine