Biotransformation and elimination of 14C-flecainide acetate in humans.
Biotransformation and elimination of 14C-flecainide acetate in humans.
复制标题
人体中 14C-醋酸氟卡尼的生物转化和消除。
DOI：
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发表时间：
1984
影响因子：
3.9
通讯作者：
G. J. Conard
中科院分区：
文献类型：
--
作者：
R. Mcquinn;G. Quarfoth;J. Johnson;E. H. Banitt;S. Pathre;S. F. Chang;R. Ober;G. J. Conard
在4名健康受试者中研究了一种新的抗肿瘤药14 C-醋酸氟卡尼的代谢，单次口服200 mg后。尿液中放射性的累积回收率范围为81 - 90%（平均值，86%），粪便中为4 - 6%（平均值，5%）;因此，氟卡尼似乎不会经过广泛的胆汁排泄，除非在胆汁消除后发生重吸收。原型氟卡尼在尿液中的累积排泄量范围为剂量的35%至50%（平均42%），并在给药后72小时基本完成。在给药后2至3 h达到放射性（524至848 ng eq/ml）和原型氟卡尼（214至281 ng/ml）的血浆峰水平。原型氟卡尼从血浆中消失的平均半衰期约为16小时;血浆中总代谢物的消失仅略慢。放射性监测TLC分析显示，尿液中含有两种主要代谢物和两种或三种次要代谢物;两种主要代谢物均广泛结合。通过与参比化合物的TLC、NMR和质谱比较，发现两种主要的尿液代谢产物为间-O-脱烷基氟卡尼和氟卡尼的间-O-脱烷基内酰胺。尿液中的大部分放射性由氟卡尼和两种主要代谢产物产生。
The metabolism of 14C-flecainide acetate, a new antiarrhythmic, was investigated in four healthy human subjects, after a single, 200-mg oral dose. The cumulative recovery of radioactivity ranged from 81 to 90% (mean, 86%) in urine and from 4 to 6% (mean, 5%) in feces; thus, flecainide does not appear to undergo extensive biliary excretion, unless reabsorption occurs after biliary elimination. The cumulative excretion in urine of unchanged flecainide ranged from 35 to 50% (mean, 42%) of the dose and was essentially complete by 72 hr postdose. Peak plasma levels of radioactivity (524 to 848 ng eq/ml) and of unchanged flecainide (214 to 281 ng/ml) were attained at 2 to 3 hr postdose. The average half-life for the disappearance of unchanged flecainide from plasma was about 16 hr; disappearance of total metabolites from plasma was only slightly slower. Radiomonitored TLC analysis showed that urine contained two major metabolites and two or three minor ones; both major metabolites were extensively conjugated. By TLC, NMR, and mass spectral comparisons to reference compounds, the two major urinary metabolites were shown to be meta-O-dealkylated flecainide and the meta-O-dealkylated lactam of flecainide. Most of the radioactivity in urine was accounted for by flecainide and the two major metabolites.
每日两次服用氟卡尼可抑制难治性室性心律失常。
DOI：
10.1016/0002-9149(81)90331-3
发表时间：
1981
期刊：
The American journal of cardiology
影响因子：
--
作者：
Duff,HJ;Roden,DM;Maffucci,RJ;Vesper,BS;Conard,GJ;Higgins,SB;Oates,JA;Smith,RF;Woosley,RL
通讯作者：
Woosley,RL