Hawkins D R, Chasseaud L F, Weston K T
Eur J Drug Metab Pharmacokinet. 1980;5(3):145-52. doi: 10.1007/BF03189458.
The major proportion of oral doses of 14C-mecinarone was excreted in the faeces by rat, dog and man, and in all species the faecal metabolites were more polar than mecinarone and the O-desmethyl reference compounds. Rat faecal extracts contained two major components each accounting for about 30-40% of the radioactivity. Dog and human faecal extracts contained some mecinarone but also three major, more polar components, two of which corresponded to the rat metabolites. Rat bile contained three major components and dog bile two components. One of the components in both bile samples was shown to be a conjugate of O-desmethyl-mecinarone. Besides mecinarone human urine contained a component corresponding to the phenol resulting from 0-demethylation in the p-methoxycinnamoyl group. The same two compounds were also detected in human plasma. The two major components in rat and dog faecal extracts gave mass spectra identical to mecinarone and the p-hydroxycinnamoyl derivative (O-desmethyl-mecinarone). It is postulated that these thermally-labile metabolites were formed by nucleophilic addition of a substituent to the alpha, beta-unsaturated ketone. It has been demonstrated in vitro that mecinarone forms a glutathione conjugate. The metabolites may be compounds of this type where the glutathione moiety has been degraded in the gastrointestinal tract.
大鼠、狗和人类口服14C-美西萘酮后，大部分剂量经粪便排泄。在所有物种中，粪便代谢产物的极性均比美西萘酮和O-去甲基参考化合物更高。大鼠粪便提取物含有两个主要成分，各占放射性的约30-40%。狗和人类粪便提取物含有一些美西萘酮，但也含有三个主要的、极性更高的成分，其中两个与大鼠代谢产物相对应。大鼠胆汁含有三个主要成分，狗胆汁含有两个成分。两个胆汁样本中的一个成分被证明是O-去甲基美西萘酮的结合物。除美西萘酮外，人类尿液中含有一种成分，对应于对甲氧基肉桂酰基0-去甲基化产生的酚。在人类血浆中也检测到了相同的两种化合物。大鼠和狗粪便提取物中的两个主要成分的质谱图与美西萘酮和对羟基肉桂酰衍生物（O-去甲基美西萘酮）相同。据推测，这些热不稳定代谢产物是通过亲核取代基加成到α,β-不饱和酮上形成的。体外实验已证明美西萘酮可形成谷胱甘肽结合物。这些代谢产物可能是这种类型的化合物，其中谷胱甘肽部分在胃肠道中已被降解。
