Aubets J, Cardenas A, Salva M, Jansat J M, Martinez-Tobed A, Palacios J M
Department of Pharmacokinetics and Drug Metabolism, Almirall Prodesfarma SA, Barcelona, Spain.
Xenobiotica. 2006 Sep;36(9):807-23. doi: 10.1080/00498250600802508.
Almotriptan is a new highly potent selective 5-HT1B/1D receptor agonist developed for the treatment of migraine, and the disposition of almotriptan in different animal species is now addressed in the current study. Almotriptan was well absorbed in rats (69.1%) and dogs (100%) following oral treatment. The absolute bioavailability was variable reflecting different degrees of absorption and first-pass metabolism (18.7-79.6%). The elimination half-life was short and ranged between 0.7 and 3 h. The main route of elimination of almotriptan was urine with 75.6% and 80.4% of the dose recovered over a 168-h period in rats and dogs, respectively. The gamma-aminobutyric acid metabolite formed by oxidation of the pyrrolidine ring was the main metabolite found in urine, faeces, bile, and plasma of rats and in monkey urine. By contrast, the unchanged drug, the indole acetic acid metabolite formed by oxidative deamination of the dimethylaminoethyl group, and the N-oxide metabolite were the main metabolites in dog.
阿莫曲坦是一种新开发的用于治疗偏头痛的高效选择性5-HT1B/1D受体激动剂，本研究探讨了阿莫曲坦在不同动物物种中的处置情况。口服给药后，阿莫曲坦在大鼠（69.1%）和犬（100%）体内吸收良好。绝对生物利用度各不相同，反映出吸收和首过代谢程度的差异（18.7-79.6%）。消除半衰期较短，在0.7至3小时之间。阿莫曲坦的主要消除途径是尿液，在大鼠和犬中，分别在168小时内回收了75.6%和80.4%的给药剂量。由吡咯烷环氧化形成的γ-氨基丁酸代谢物是在大鼠的尿液、粪便、胆汁和血浆以及猴尿中发现的主要代谢物。相比之下，原形药物、由二甲氨基乙基氧化脱氨形成的吲哚乙酸代谢物以及N-氧化物代谢物是犬体内的主要代谢物。
