title: In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver preparations using liquid chromatography/electrospray mass spectrometry.
abstract: The in vitro metabolism of a new erectogenic, DA-8159, has been studied by LC with UV detection and on-line LC-electrospray mass spectrometry using rat hepatic microsomal incubation and rat liver perfusion. Both rat liver microsomal incubation of DA-8159 in the presence of NADPH and single-pass liver perfusion of DA-8159 resulted in the formation of three metabolites (M1-3). M1 was tentatively identified as hydroxy-DA-8159. M2 and M3 were identified as N-demethyl-DA-8159 and 5-(2-propyloxy-5-aminosulphonylphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (DA-8164), respectively, on the basis of LC-MS/MS analysis with authentic standards. Rat CYP2D1 was a major isozyme for the formation of hydroxy-DA-8159 and N-demethyl-DA-8159. CYP2C12 and CYP1A1 catalysed the oxidation of DA-8159 to DA-8164.
authors.affiliation: Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Hee-Yong
authors.initials: HY
authors.lastname: Lee
authors.forename: Dong Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D011743:Pyrimidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013449:Sulfonamides; D000096926:Benzenesulfonamides
chemical_list: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D003577:Cytochrome P-450 Enzyme System; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D011743:Pyrimidines; D013449:Sulfonamides; C517384:Pde5a protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides