摘要
目的研究不同给药途径后蝙蝠葛碱在大鼠体内的药代动力学特征。方法以大鼠为实验对象，经灌胃及静脉注射两种途径给药，采用ＲＰ－ＨＰＬＣ法测定各组织及体液中药物浓度。结果静注蝙蝠葛碱在大鼠体内药代动力学为二室开放模型，符合一级动力学线性消除过程。灌胃给药后大鼠血药浓度低，峰浓度小于１ｍｇ·Ｌ－１，且血药浓度－时间曲线呈明显双峰现象。其绝对生物利用度约为１６．６％。蝙蝠葛碱经两种给药途径后药物在各组织器官中均有分布，且在同一时间内各组织含量明显高于血药浓度。静注后以肺组织含量最高，而灌胃给药后以胃、肠、肝组织含量最高。４８ｈ尿粪累积排泄３１．２２％。给药后不同时间点胃肠道各段药物残余量研究结果提示胃肠循环的存在。结论蝙蝠葛碱口服用药生物利用度较低，血药浓度一时间曲线呈双峰现象，该药在生物体内分布广泛，可由尿液及粪便排泄，也可从胆汁分泌，初步实验结果提示胃肠循环可能是药时曲线双峰现象的主要原因。
AIM To study the pharmacokinetic characters of dauricine(Dau) in rats after different administration ways. METHOD RP-HPLC method was used in the study. RESULT The results indicated that the plasma C-T curve conform to two- compartment open model after iv. The plasma concentra- tion of Dan in rats for ig Dan 150 mg.kg-1 is low, less than 1 mg.L-1 of peak concentration. The abso lute bioavailibility is about 16 .6 %. The plasma concentration-time profile shows a double-peak phe- nomenon The time taken to reach the peak is about 15 min after ig and the trough time is 3 h. The plasma concentration increased again in 4 h to form the second peak. The studies suppose a stomach-intestine recirculation of Dan is the major reason for doublepeak phenomenon. Dau has a wide distribution in rat body. It lies in all tissues and organs in both adminastration ways. The tissue Dan concentration are hundreds times higher than that in plasma concurrently. Faces is the main route whereby Dau are excreted from the rats after ig 150 mg. kg-1. The excreted percentage through feces is 26 .29 %, while through urine is 4.93%. The total amount is 31.22% after 48h of oral administration of Dau. The study of the mean percentage of the dose remaining in stomach, small intestine, large intestine and whole GI tract from each rat sacrificed at different times after oral administration of Dan suggest the stomach-intestine circle. CONCLUSION The bioavailibility of Dau is low. The plasma drug concentration versus time curve shows an innormal double-peak phenomenon. Dau can distribute abroadly to almost all kinds of the tissues in rats. The ban excretion routes are through feces and urine. The pilot study suggests that stomach-intestine circle be the main ran for the innormal double-peak phenomenon.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2001年第2期225-229,共5页
Chinese Pharmacological Bulletin
