Metabolism and excretion of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]-pyrimidin-4-one (SK3530) in rats

摘要: The in vitro and vivo metabolism of a novel PDE 5 inhibitor, SK3530, was investigated rats. Bile, plasma, feces, urine liver samples were collected analyzed using high-performance liquid chromatography (HPLC) system equipped with ultraviolet (UV), mass spectrometric radioactivity detectors. After single oral administration, the mean radiocarbon recovery 92.32 ± 6.26%, 91.25 ± 6.25 1.07 ± 0.21% feces urine, respectively. biliary excretion for first 24 h period approximately 38.82%, suggesting that SK3530 is cleared by hepatobiliary excretion. In incubation rat human microsomes resulted formation twelve ten metabolites, extensively metabolized to twenty different including three glucuronide sulfate conjugates structures these metabolites elucidated based on MSn spectral analyses. Six major metabolic pathways identified rat: N-dealkylation oxidation hydroxyethyl moiety; N,N-deethylation hydroxylation piperazine ring; propyl group conjugation. An additional metabolite due aromatic also hepatic microsomes. Copyright © 2007 John Wiley & Sons, Ltd.