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- W2437946626 abstract "The metabolism of L-691,121 (I), a class III antiarrhythmic agent, was studied in vivo in rats and dogs and in vitro by using liver S9 or slices from these species and humans. After oral doses of [14C]I to rats (5 mg/kg) and dogs (1 mg/kg), urinary recoveries of label were, respectively, 6% and 28%. Biliary excretion (0-24 hr) accounted for 68% of a 5 mg/kg, po dose in rats and 19% of a 10 mg/kg dose, po in dogs. Metabolites were identified by application of FAB/MS, NMR, and diode-array UV spectroscopy. The major dog metabolites were the secondary alcohol (II) produced by carbonyl reduction and its glucuronide conjugate (III). It was estimated that II and III represented 24 and 36%, respectively, of the dog biliary radioactivity. After a 50 mg/kg dose of I, II represented approximately 50% of the dog urinary label. A minor metabolite (IV) in dog urine was produced by reduction and loss of N-substitution. There were species differences in that, relative to dogs, II represented a much smaller fraction of the excreted dose in rats and there was no evidence for excretion of III in rats. N-Dealkylated I (V) was excreted, along with IV in rat bile. Dog liver slices and S9 fractions were most efficient (relative to human and rat liver tissues) at reducing I to II. Metabolic reduction of I to II was highly stereoselective and yielded the (-)-antipode as determined by chiral chromatography." @default.
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- W2437946626 date "1993-05-01" @default.
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- W2437946626 title "In vivo and in vitro metabolism studies on a class III antiarrhythmic agent." @default.
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