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

Arzneimittelforschung. 1989 Jul;39(7):805-8.

Abstract

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 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

Substances

  • Anti-Ulcer Agents
  • Benzoxepins
  • KW 5805