三七总皂苷肠溶胶囊在比格犬体内的药代动力学

目的探讨三七总皂苷(PNS)肠溶胶囊在比格犬体内的药代动力学。方法比格犬采用随机交叉给药方案,口服PNS肠溶胶囊86.2 mg·kg-1或血栓通胶囊111.8 mg·kg-1后,用反相高效液相色谱法同时测定犬血浆中三七皂苷R1、人参皂苷Rg1和Rb1的血药浓度,采用3P97药动学软件计算药动学参数和基于曲线下面积(AUC0-∞)自定义权重系数整合血药浓度后的药动学参数。结果与参比制剂血栓通比较,受试制剂PNS R1、Rg1、Rb1的达峰时间延长:R10.18±0.09 vs(0.16±0.06)h,Rg12.03±0.76 vs(1.74±0.27)h,Rb1 0.76±0.39 vs(0.74±0.17)h;吸收延迟时间延长:R1 0.96±0.16 vs(0.50±0.11)h,Rg10.87±0.05 vs(0.02±0.01)h,Rb10.92±0.12 vs(0.44±0.07)h,3种成分及其整合后PNS的相对生物利用度分别为248.41%,107.19%,152.94%和155.31%。整合后,血栓通胶囊和PNS肠溶胶囊的主要药动学参数分别为:AUC0→t39.17±3.89 vs(46.91±3.86)mg.L-1.h,Lag时间0.45±0.18 vs(0.92±0.13)h,tmax0.74±0.17 vs(0.77±0.13)h,Cl(3.84±0.24 vs 1.84±0.97 L.kg-1.h-1)。结论本实验制备的PNS肠溶胶囊能提高PNS的口服生物利用度。

Pharmacokinetics of Panax notoginseng saponins enteric-coated capsules in Beagle dogs

OBJECTIVE To investigate pharmacokinetics of Panax notoginseng saponins(PNS) in Beagle dogs.METHODS PNS enteric-coated capsules 86.2 mg·kg-1 and Xueshuantong capsules 111.8 mg·kg-1 were administered to dogs according to an open randomized crossover design.The plasma concentration of notoginsenoside R1,ginsenoside Rg1 and Rb1 was determined by RP-HPLC.Pharmacokinetic parameters were calculated by 3P97 software so were those after the integration of blood concentration based on AUC0→∞.RESULTS Compared with reference preparation,tmax of test preparation R1,Rg1,Rb1 increased: 0.18±0.09 vs(0.16±0.06)h for R1,2.03±0.76 vs(1.74±0.27)h for Rg1,0.76±0.39 vs(0.74±0.17)h for Rb1;Lag times were prolonged: 0.96±0.16 vs(0.50±0.11)h for R1,0.87±0.05 vs(0.02±0.01)h for Rg1,0.92±0.12 vs(0.44±0.07)h for Rb1.The relative bioavailability of R1,Rg1,Rb1 and PNS was 248.41%,107.19%,152.94% and 155.31%,respectively.After integration,the main pharmacokinetic parameters of Xueshuantong capsules and PNS enteric-coated capsules respectively were: AUC0→t 39.17±3.89 vs(46.91±3.86)mg·L-1·h,Lag times 0.45±0.18 vs(0.93±0.13)h,tmax 0.74±0.17 vs(0.77±0.13)h,Cl3.84±0.24 vs(1.84±0.97)L·kg-1·h-1.CONCLUSIONPNS enteric-coated capsule can improve the oral bioavailability of PNS.