利用稳定同位素研究氯苯那敏在大鼠和人体内的代谢。

Metabolism of chlorpheniramine in rat and human by use of stable isotopes.

Kasuya F, Igarashi K, Fukui M

Faculty of Pharmaceutical Science, Kobegakuin University, Kobe, Japan.

Xenobiotica. 1991 Jan;21(1):97-109. doi: 10.3109/00498259109039454.

Abstract

The metabolism of chlorpheniramine (I) was examined in vivo in rats and a human volunteer; in the rats a stable isotope was used. 2. In addition to the unchanged drug (I) and the N-demethylated metabolites (II and III), nine further metabolites were identified in rat urine, four of which were also found in human urine. Chlorpheniramine N-oxide (IV), 3-(p-chlorophenyl)-3-(2-pyridyl) propanol (V), 3-(p-chlorophenyl)-3-(2-pyridyl)-N-acetylaminopropane (VII) and 3-(p-chlorophenyl)-3-(2-pyridyl)-propionic acid (XIII) were identified in rat and human urine. 3. The hydroxylated metabolites of the pyridyl ring of the unchanged drug, II, V and VII, and the glucuronide of XIII were identified only in rat urine. XIII was found in rat urine as long as 6 days after the last dose.

摘要

在大鼠和一名人类志愿者体内对氯苯那敏（I）的代谢进行了研究；在大鼠实验中使用了稳定同位素。2. 除了未变化的药物（I）和N - 去甲基代谢物（II和III）外，在大鼠尿液中还鉴定出另外九种代谢物，其中四种在人类尿液中也被发现。氯苯那敏N - 氧化物（IV）、3 - （对氯苯基）-3 - （2 - 吡啶基）丙醇（V）、3 - （对氯苯基）-3 - （2 - 吡啶基）-N - 乙酰氨基丙烷（VII）和3 - （对氯苯基）-3 - （2 - 吡啶基）丙酸（XIII）在大鼠和人类尿液中均被鉴定出。3. 未变化药物吡啶环的羟基化代谢物II、V和VII以及XIII的葡萄糖醛酸苷仅在大鼠尿液中被鉴定出。在最后一次给药后长达6天的大鼠尿液中都能发现XIII。