摘要
用放射性同位素的方法研究了丁基苯肽（ＮＢＰ）在大鼠体内代谢，并对代谢产物进行了鉴定。结果表明，大鼠ｉｇ３ＨＮＢＰ后２４ｈ，从尿和粪中排出的放射性分别为ｉｇ剂量的５５２％和１８５％，排除了药物蓄积在体内的可能性；用高效液相色谱法分离、纯化了丁基苯酞的两个主要的体外代谢产物代Ｉ和代Ｉ，根据代Ｉ和代ＩＩ的波谱数据（ＵＶ，１ＨＮＭＲ，ＭＳ）确定了它们的化学结构；薄层色谱（ＴＬＣ）证明丁基苯酞的体内代谢产物同样有代Ｉ和代Ｉ，并且也是两个主要的代谢产物；大鼠ｉｇ３ＨＮＢＰ后１ｈ，脑中原型药与代谢物的比例为１∶１，而且只发现有代Ｉ，未发现有代Ｉ，推测代Ｉ很有可能是活性代谢产物。
The metabolites of dl 3 n butyphthalide(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 ig 3H NBP, the total radioactivity excreted in urine and feces was 73 7% of the dose. Comparing with previous study, within 72 h following ig 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(ig 3H NBP) were analizied 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 ig 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.
出处
《药学学报》
CAS
CSCD
北大核心
1997年第9期641-646,共6页
Acta Pharmaceutica Sinica
基金
国家科委1035工程重大项目
