Wang C H, Feng Y P, Wu Y L
Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050.
Yao Xue Xue Bao. 1997 Sep;32(9):641-6.
The metabolites of dl-3-n-butylphthalide(NBP), a novel drug with promising protective action against cerebral ischemia, was studied in rats. Two main in vitro metabolites of NBP, M I and M II, were isolated and purified from rat liver microsome incubating system by using HPLC. The structure elucidation was mainly accomplished by spectral studies(UV, 1H-NMR, MS). Within 24 h following i.g. 3H-NBP, the total radioactivity excreted in urine and feces was 73.7% of the dose. Comparing with previous study, within 72 h following i.g. NBP, the total prototype drug excreted in urine and feces was 2.53% of the dose. This result excludes the possibility that NBP accumulates in vivo. The urine and brain homogenate of the rats(i.g. 3H-NBP) were analyzed by TLC. M I and M II were found in urine and M I was found in brain only. Furthermore, the ratio of radioactive M I to proptype drug was 1:1 in rat brain within 1 h following i.g. 3H-NBP. So, M I and M II were supposed to be the two main in vivo metabolites of NBP and M I might be an active metabolite.
对一种对脑缺血具有潜在保护作用的新型药物dl-3-正丁基苯酞（NBP）的代谢产物在大鼠体内进行了研究。通过高效液相色谱法从大鼠肝微粒体孵育系统中分离并纯化出NBP的两种主要体外代谢产物M I和M II。结构解析主要通过光谱研究（紫外、氢核磁共振、质谱）完成。灌胃3H-NBP后24小时内，尿液和粪便中排出的总放射性为给药剂量的73.7%。与之前的研究相比，灌胃NBP后72小时内，尿液和粪便中排出的总原型药物为给药剂量的2.53%。该结果排除了NBP在体内蓄积的可能性。通过薄层色谱法分析大鼠（灌胃3H-NBP）的尿液和脑匀浆。在尿液中发现了M I和M II，仅在脑中发现了M I。此外，灌胃3H-NBP后1小时内，大鼠脑中放射性M I与原型药物的比例为1:1。因此，推测M I和M II是NBP的两种主要体内代谢产物，且M I可能是一种活性代谢产物。
