Larsson H, Lund J
Acta Pharmacol Toxicol (Copenh). 1981 May;48(5):424-32. doi: 10.1111/j.1600-0773.1981.tb01642.x.
The metabolism of femoxetine, a serotonin uptake inhibitor, has been investigated in rats, dogs, monkeys, and human subjects using two 14C-femoxetine compounds with labelling in different positions. The metabolic pathways were oxidation (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolised, and the same metabolites were found in urine from all four species. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N-oxide than monkey and man, while most of the radioactivity (60-100%) in these two species was excreted as two hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in these two species as one metabolite, formed by demethylation of a methoxy group. A demethylation of a N-CH3 group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0 to 18% of the dose between individuals. Most of the radioactivity was excreted with the faeces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in the metabolite pattern. No dose dependency was observed in any of the three animal species investigated.
已使用两种在不同位置标记的14C-非莫西汀化合物，在大鼠、狗、猴子和人类受试者中研究了5-羟色胺摄取抑制剂非莫西汀的代谢情况。代谢途径为氧化（和葡糖醛酸化）及去甲基化，这两种反应很可能都在肝脏中发生。几乎所有非莫西汀都发生了代谢，且在所有四个物种的尿液中都发现了相同的代谢物。尿液中排泄的放射性物质只有一小部分未被鉴定出来。大鼠和狗排泄的N-氧化物比猴子和人类多，而这两个物种中大部分放射性物质（60%-100%）以两种羟基代谢物的形式排泄。猴子和人类的代谢模式非常相似。在这两个物种中，约50%以一种由甲氧基去甲基化形成的代谢物形式排泄。N-CH3基团的去甲基化形成了一种活性代谢物——去甲非莫西汀。人类尿液中这种代谢物的排泄量在个体之间占剂量的0%至18%不等。大鼠和狗的大部分放射性物质随粪便排泄，而猴子和人类则将大部分放射性物质通过尿液排泄。排泄途径的这种差异可能由代谢物模式的差异来解释。在所研究的三种动物物种中均未观察到剂量依赖性。
