Neidlein R, Volland C, Strein K
Pharmaceutical-Chemical Institute of the University of Heidelberg, Fed. Rep. of Germany.
Arzneimittelforschung. 1990 Jan;40(1):27-31.
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.
使用经口服和静脉注射给予的14C标记药物，在犬类动物中检测了多沙米诺（N-甲基-N-(2-羟基-3-苯氧基丙基)-11-(2-氨基乙基)-6,11-二氢二苯并[b,e]噁庚因，富马酸中性盐；BM 10.188）的药代动力学行为。给药后1小时达到最大血浆浓度，表明多沙米诺吸收相对较快。静脉注射和口服给药后总放射性的下降呈现两个阶段，消除半衰期分别为1.33小时和1.55小时，以及24.05小时和21.05小时。多沙米诺的生物利用度约为60%。未改变药物的血浆水平表明多沙米诺很快被消除和代谢。在96小时的检测期内，静脉注射后，多沙米诺及其代谢产物通过尿液和粪便的消除量占给药量的76.5%，口服给药后占给药剂量的44.1%。放射性的主要消除途径是粪便（分别占剂量的61.5%和31.2%），而通过尿液的消除量分别占剂量的15.0%和12.9%。
