E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr1, N-methyl-Arg7- D-Leu8] Dyn A (1-8) ethylamide. Its biochemical stability against enzymatic degradation in vitro in human and rhesus monkey blood, and in vivo in rhesus monkey blood was studied using matrix-assisted laser desorption/ionization mass spectrometry. In vitro studies were carried out in freshly drawn human and rhesus monkey blood, incubated at 37°C for various time periods. In vivo studies were conducted by E-2078 i.v. injection to rhesus monkeys, and blood samples were collected at various time points after the injection. It was found that E-2078 was stable against enzymatic degradation in vitro in freshly drawn human and rhesus monkey blood. Minor biotransformation products from E-2078, such as E (1-4), E (1-5) and E (3-6), were detected in vitro in some human and rhesus monkey blood, but they made up less than 5% of the total starting E-2078 peptide. No biotransformation products were detected in the blood samples from in vivo studies. The apparent half-life of elimination of E-2078 in vivo from the rhesus monkey blood was determined to be 44.0 min.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Mar 1997|
ASJC Scopus subject areas
- Molecular Medicine