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Pharmacokinetics of soluble epoxide hydrolase inhibitors in canine, rodent, feline, and primate species
Author(s) -
Tsai HsingJu,
Liu Jun Yan,
Hwang Sung Hee,
Kasagami Takeo,
Kim In Hae,
Jones Paul D.,
Morisseau Christophe,
Hammock Bruce D.
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.479.17
Subject(s) - in vivo , potency , pharmacology , pharmacokinetics , epoxide hydrolase 2 , in vitro , chemistry , enzyme , biochemistry , medicine , biology , microbiology and biotechnology
Soluble epoxide hydrolase inhibitors (sEHi) have been shown the therapeutic effects on hypertension, sepsis, and hypertrophy in different animal models. However, the inhibitors were hard to formulate which limits the administration methods, and their bioavailabilities were low leading to high dose treatments for observing some biological effects in vivo. Thus, compounds having improved physical properties and similar potency were recently synthesized. However, it is unknown the compounds perform consistent in vitro and in vivo among species. Herein, the results showed that the in vitro potency of some compounds were different among species, especially with dog and cat enzymes. Further, we also described the pharmacokinetic profiles in vivo of different animals. In summary, the inhibitors have different potency and pharmacokinetic profiles among species. With the information, sEHi will be invaluable tools to investigate the role of sEH and eicosanoids in biological systems. This work was supported in part by NIEHS Grant R37 ES02710, NIEHS SBRP Grant P42 ES04699, and NIEHS CEHS Grant P30 ES05707.