三七总皂苷肠溶微囊的药代动力学及体内外相关性

目的:考察三七总皂苷(panax notoginseng saponins,PNS)肠溶微囊在Beagle犬体内的释药行为及其体内外相关性研究。方法:采用双周期交叉试验设计,6只健康Beagle犬口服市售血栓通胶囊或自制PNS肠溶微囊(胶囊型)后,用HPLC法测定血药浓度,计算两制剂的药代动力学参数,进行生物利用度比较,并对体外累积释放度和体内累积吸收百分率进行线性回归。结果:自制PNS肠溶微囊对市售血栓通胶囊的相对生物利用度为三七皂苷R1(R1)313.63%,人参皂苷Rb1(Rb1)314.35%,人参皂苷Rg1(Rg1)202.03%,上述3成分在体内的平均滞留时间均延长,R1,Rb1和Rg1的体内外相关系数分别为0.866 4,0.958 0和0.719 2。结论:自制PNS肠溶微囊与市售血栓通胶囊相比生物利用度更高,Rb1体内外相关性较好,可用一定的体外释放条件进行体内行为的预测,R1和Rg1体内外相关性较差。

Pharmacokinetics and correlation between in vivo absorption and in vitro release of panax notoginseng saponins enteric microcapsule

Objective:To determine the pharmacokinetics of panax notoginseng saponins(PNS) enteric microcapsule in Beagle dogs and study the correlation between in vivo absorption and in vitro release of PNS enteric microcapsule.Methods:The relative bioavailability of PNS enteric microcapsule(capsules) to Xueshuantong capsule was evaluated in six Beagle dogs according to a randomized two-period crossover design.The plasma concentrations of the two preparations were determined by HPLC method.Pharmacokinetic parameters were calculated.The correlation between dissolution rate and absorption percentage was investigated.Results:The relative bioavailabilities of notoginsenoside R1(R1),ginsenoside Rb1(Rb1)and ginsenoside Rg1(Rg1)in PNS enteric microcapsule to those in Xueshuantong capsule were 313.63%,314.35% and 202.03%,respectively.The mean residence time of the three active components in PNS enteric microcapsule was longer than referenced preparation in vivo.The in vitro-in vivo correlation coefficients of R1,Rb1 and Rg1 were 0.866 4,0.958 0 and 0.719 2,respectively.Conclusion:The bioavailability of PNS enteric microcapsule is higher than Xueshuantong capsule.There is good correlation for Rb1 and a bad correlation for R1 and Rg1 between in vivo absorption and in vitro release.The absorption characteristics of R1 and Rb1 in vivo can be predicted according to release in vitro under certain conditions.