氯硝安定在生物体内的代谢

Studies on metabolic transformation of clonazepam in the body

目的推测氯硝安定在生物体内的主要代谢方式,检测其代谢产物。方法取5只Wistar大鼠,连续3d给每只大鼠灌胃氯硝安定(剂量分别为1、2、2mg),收集灌胃后24h内尿液;给3只大鼠各灌胃2mg氯硝安定,2h后处死,取血液和肝组织等检材;收集3名口服5mg氯硝安定的志愿者24h内尿液。分别对不同检材进行处理后,气相色谱/质谱联用(GC/MS)检测。结果在大鼠阳性尿液和志愿者阳性尿液中,均检出7-乙酰氨基氯硝安定和7-氨基氯硝基安定;在大鼠血液中,主要检出氯硝安定和7-氨基氯硝基安定;在大鼠肝组织中,主要检出7-乙酰氨基氯硝安定,还有少量7-氨基氯硝安定和氯硝安定。结论氯硝安定进入生物体后,其7位硝基被还原为氨基,氨基接着被乙酰化,形成7-氨基氯硝基安定和7-乙酰氨基氯硝安定代谢物,其中7-乙酰氨基氯硝安定为主要代谢物。

Objective To study the metabolites and metabolic process of clonazepam in the body.Methods Five wistar rats were gavaged （ each with 1, 2,2mg/d dose ,respectively）for three consecutive days, collected the urine within 24h. Three wistar rats each gavaged 2rag elonazepam were killed after 2h, the blood and the liver specimens were collected. The 24 hour urine of the human volunteers after oral administration of 5mg clonazepam was also collected. After pretreatment, all the samples were analyzed by gas chromatography-mass spectrometry. Results 7-Acetylaminoclonazepam and 7-aminoclonazepam were identified as clonazepam metabolites both in rat and human urine. It was found that clonazepam and 7-aminoclonazepam mainly existed in the blood of the rats while both 7-acetylaminoclonazepam and 7-aminoclonazepam in the liver of the rats. Conclusion The results suggest that, in the metabolic process, the nitro-group on clonazepare is first reduced to amino group, and then acetylated. 7-Acetylaminoclonazepam is the main metabolite in urine.