Identification of major metabolites of the catechol-O-methyltransferase inhibitor entacapone in rats and humans.

摘要: Metabolites of entacapone [(E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide++ +], a potent inhibitor catechol-O-methyltransferase, were isolated from human and rat urine. After hydrolysis glycosides sulfates, four eight metabolites identified, in addition to unchanged by HPLC with diode-array UV detection, electron ionization mass spectrometry, IR spectroscopy. In man 10% an oral dose was excreted urine during 8 hr. The glucuronides its (Z)-isomer represented about 70 25% the urinary metabolites, respectively. two less abundant formed through cleavage or reduction side chain carbon-carbon double bond, also erythrocyte incubation. only phase I metabolite found plasma. nitro group seems hinder methylation catechol hydroxyls man, because no products detected. Twenty-four hr after iv administration 14C-labeled rats, over 50% feces approximately 35% extensively metabolized Entacapone mainly as sulfates most glucuronide entacapone. Unchanged, N-dealkylated, O-methylated entacapone, 3,4-dihydroxy-5-nitrobenzaldehyde both plasma rats. Two minor bond acetylation amino resulting reduction.