摘要
目的研究苦参碱在健康志愿者近端小肠内定点释放后的药代动力学特征。方法用自主研制的遥控释药胶囊系统,将200mg苦参碱定位释放于志愿者的近端小肠内。用高效液相色谱法,以槐果碱为内标,甲醇-水-乙二胺(70∶30∶0.02)为流动相,测定志愿者血浆中苦参碱的含量。采用3p87程序计算药代动力学参数。结果近端小肠定点释放苦参碱的药代动力学符合二室开放模型,Cmax为10.52μg/ml,Tmax为2.08h,T1/2α和T1/2β分别为0.90h和9.02h,AUC(0-t)为91.90μg·h/ml。结论苦参碱在健康人近端小肠段定位释放后,小肠对苦参碱有明显的吸收且吸收过程呈二室模型分布。
Objective To investigate the pharmacokinetics of remote controlled capsule for matrine in the proximal small intestine of healthy volunteers and obtain the standard pharmacokinetic parameters. Methods A total of 200 mg matrine was delivered in the proximal small intestine of 12 healthy male volunteers by re- mote controlled capsule system, which made by our work group. Blood sample of 3 ml for each time was harvested respectively in0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, 30.0 and 36.0 h after the matrine was released when the capsule entered into the proximal small intestine. HPLC-UV was used to measure matrine concentrations in the plasma by adding an internal standard （sophocarpine）. Methanol-water-ethylenediamine （70： 30： 0.02） was used as the mobile phase. The main parameters were calculated by 3p87 pharmacokinetic program. Results The martine pharmacokinetics conforms to a two-compartment open model after a single delivery of martine at a dose of 200 mg in upper small intestine of healthy volunteers. The main parameters were as follows： Cmax was 10.52 μg/ml Tmax was 2.08 h, T1/2α,was 0.90 h, T1/2βwas 9.02 h, K12 was 0.21 h, K21was 0. 53 h, K10 was 0. 12 h, MRT（0-t） was 11. 56 h and AUC（0-t） was 91. 90 μg·h/ml. Conclusion There is an effective absorption when matrine is site-specific delivered in the proximal small intestine. The process in vivo fits well to two compartment open model.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第6期529-532,共4页
Journal of Third Military Medical University
基金
国家自然科学基金(30700160)
国家高技术研究发展计划(863计划
2004AA404012)
中国博士后科学基金(20070420718)
重庆市自然科学基金(CSTC2006BA5005)~~
关键词
缓释制剂
苦参碱
投药
局部
药代动力学
色谱法
高效液相
sustained-release preparations
administration, topical
matrine
pharmacokinetics
chromatography, high performance liquid
