Tolerance and pharmacokinetics of a new antiulcer compound in man after single oral doses

• Published in: Arzneimittel-Forschung Vol. 39; no. 7; p. 805
• Main Authors: Uckert, B, Kobayashi, S, Maier-Lenz, H
• Format: Journal Article
• Language: English
• Published: Germany 01.07.1989
• Subjects: Adult; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - adverse effects; Anti-Ulcer Agents - pharmacokinetics; Benzoxepins - administration & dosage; Benzoxepins - adverse effects; Benzoxepins - pharmacokinetics; Blood Pressure - drug effects; Body Temperature - drug effects; Chromatography, Gas; Chromatography, High Pressure Liquid; Double-Blind Method; Electrocardiography; Humans; Male; Pulse - drug effects
• ISSN: 0004-4172

5-[(2-Diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride (KW-5805) is a new antiulcer compound, which was effective in animal studies by increasing gastric mucus and stimulating defensive factors such as glucosamine-synthesizing enzymes rather than by inhibiting aggressive factors. In this placebo-controlled, double-blind study the tolerability and pharmacokinetics of KW-5805 have been evaluated first time in man. Single oral doses of 2.5 to 320 mg were administered to 3 healthy young male subjects per dose level. One additional subject received placebo at each dose level. Plasma and urine samples were collected up to 24 h after administration and analysed gaschromatographically respectively by a high performance liquid chromatography. The mean maximum concentrations in plasma of KW-5805 occurred between 1.17 and 3.33 h after administration, independent of the dose. The half-lives of elimination varied between 6.63 and 11.9 h. 13.4-23.7, 9.6-13.4 and 6.5-11.0% of the administered dose were recovered in the urine after 24 h as unchanged substance, as monodeethylated (M-1) and as hydroxylated (M-3) metabolite, respectively. KW-5805 was not associated with any clinically significant effect on vital signs, ECG or laboratory investigations. Subjectively and objectively the substance was well tolerated in the dose range administered.