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Pharmacokinetic studies with BLX‐1026, a novel Orexin‐2 receptor agonist with anti‐obesity property, in rats
Author(s) -
Sen Ananda,
Mukherjee Aparna,
Neogi Partha,
Dey Deben,
Nag Abjijeet,
Nag Biswajit
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.922.1
Subject(s) - pharmacokinetics , agonist , receptor , in vivo , microsome , medicine , endocrinology , chemistry , orexin , in vitro , metabolism , pharmacology , biology , biochemistry , neuropeptide , microbiology and biotechnology
Orexin receptors have been implicated in non‐exercise activity thermogenesis. Increased levels of Orexin‐2 receptors have been observed in obesity‐resistant rats and decreased Orexin‐A levels observed in obese humans. BLX‐1026 is a water soluble, amino‐acid conjugated small molecule with in vitro Orexin‐2 receptor agonist activity. Phase I metabolism studies conducted with BLX‐1026 in rat, mice, dog, monkey and human liver microsomes and human liver S9 fractions show that it is stable in the liver microsomes but shows a 61% degradation in the human S9 fractions when incubated for 1 hour. In‐vivo pharmacokinetic study with BLX‐1026 was conducted in rats. It was administered at 50, 100 and 200 mg/kg, PO, and 10 mg/kg, IV, to male rats. Blood was collected for 24 hours and urine was collected for 72 hours following its administration. These were analyzed for the parent BLX‐1026 and any metabolites. The results will be presented and discussed.