Pharmacokinetics of the selective prostacyclin receptor agonist selexipag in rats, dogs and monkeys

@article{Ichikawa2018PharmacokineticsOT,
  title={Pharmacokinetics of the selective prostacyclin receptor agonist selexipag in rats, dogs and monkeys},
  author={Tomohiko Ichikawa and Tetsuhiro Yamada and Alexander Treiber and Carmela Gnerre and Kiyoko Nonaka},
  journal={Xenobiotica},
  year={2018},
  volume={48},
  pages={186 - 196}
}
Abstract 1. This study examined the pharmacokinetics, distribution, metabolism and excretion of the selective prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-33679). The compounds were investigated following oral and/or intravenous administration to intact rats, dogs and monkeys, and bile-duct-cannulated rats and dogs. 2. After oral administration of [14C]selexipag, selexipag was well absorbed in rats and dogs with total recoveries of over 90… 
Cross-species comparison of the metabolism and excretion of selexipag
TLDR
Overall, selexipag was eliminated via multiple routes in animals, including hydrolysis, oxidative metabolism, conjugation, intestinal deconjugation, and gut flora metabolism.
Simultaneous quantification and pharmacokinetic investigation of selexipag and its main metabolite ACT-333679 in rat plasma by UPLC-MS/MS method.
TLDR
The newly developed UPLC-MS/MS assay was forward successfully used to describe the pharmacokinetic profiles of selexipag and ACT-333679 in rats after oral treatment with 6.0 mg/kg selexIPag.

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