Pharmacokinetics of the partial beta-agonist doxaminol in dog

The pharmacokinetic behaviour of doxaminol (N-methyl-N-(2-hydroxy-3-phenoxy-propyl)-11-(2-amino-ethyl)-6, 11-dihydrodibenz[b,e]oxepine, neutral fumarate; BM 10.188) was examined in dogs using peroral and intravenous application of the 14C-labelled drug. The maximum plasma concentration was reached 1 h after application, indicating a relatively quick absorption of doxaminol. Decrease of total radioactivity after intravenous and peroral application is characterized by two phases, the elimination half-lives being 1.33 and 1.55 h, respectively, and 24.05 and 21.05 h, respectively. The biological availability of doxaminol was ca. 60%. The plasma levels of the unchanged drug showed that doxaminol was very rapidly eliminated and metabolized. Within the examined period of 96 h, the elimination of doxaminol and its metabolites via urine and faeces amounted to 76.5% after intravenous application, and 44.1% of the applied dose after peroral application. The major amount of radioactivity is eliminated via faeces (61.5% and 31.2% of dose, respectively) while the elimination through urine is found to be 15.0 and 12.9% of the dose, respectively.