Disposition and metabolism of almotriptan in rats, dogs and monkeys

Abstract

Almotriptan is a new highly potent selective 5-HT_1B/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 γ-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.

• Almotriptan
• disposition
• pyrrolidine ring oxidation
• deamination
• N-oxidation