Cross-species comparison of the metabolism and excretion of selexipag

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Tomohiko IchikawaKiyoko Nonaka

Abstract

1. The metabolism of the prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-333679) has been investigated in liver microsomes and hepatocytes of rats, dogs, and monkeys. MRE-269 formation is the main pathway of selexipag metabolism, irrespective of species. Some interspecies differences were evident for both compounds in terms of both metabolic turnover and metabolic profiles. The metabolism of MRE-269 was slower than that of selexipag in all three species. 2. The metabolism of selexipag was also studied in bile-duct-cannulated rats and dogs after a single oral and intravenous dose of [14C]selexipag. MRE-269 acyl glucuronide was found in both rat and dog bile. Internal acyl migration reactions of MRE-269 glucuronide were identified in an experiment with the synthetic standard MRE-6001. 3. MRE-269 was the major component in the faeces of rats and dogs. In ex vivo study using rat and dog faeces, selexipag hydrolysis to MRE-269 by the intestinal microflora is considered to be a contributory factor in rats and dogs. 4. A taurine conjugate of MRE-269 was identified in rat bile sample. Overall, selexipag was eliminated via multiple routes in animals, including hydrolysis, oxidative met...Continue Reading

References

Jan 1, 1995·Nature Medicine·P Z Zia-AmirhosseiniL Z Benet
Sep 21, 2012·Journal of Dental Research·L ZhanJ D B Featherstone
Mar 12, 2013·Pharmacological Reviews·Jack Uetrecht, Dean J Naisbitt
Sep 5, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Alexander TreiberSwen Seeland
Feb 6, 2016·Drugs·Lesley J Scott
Nov 26, 2016·European Journal of Clinical Pharmacology·Priska KaufmannJasper Dingemanse
Mar 10, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Tomohiko IchikawaKiyoko Nonaka
Jul 25, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Carmela GnerreAlexander Treiber

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Related Papers

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Tomohiko IchikawaKiyoko Nonaka
Drug Metabolism and Disposition : the Biological Fate of Chemicals
Donglu ZhangScott J Grossman
© 2022 Meta ULC. All rights reserved