复方丹参双相胶囊、复方丹参胶囊中6种有效成分在Beagle犬体内药动学比较

Comparison of in vivo pharmacokinetics of six active constituents from Compound Danshen Biphasic Capsules and Compound Danshen Capsules in Beagle dogs

目的比较复方丹参双相胶囊、复方丹参胶囊中丹参酮Ⅱ_(A)、丹酚酸B、三七皂苷R_(1)、人参皂苷Rg_(1)、人参皂苷Rb_(1)、龙脑在Beagle犬体内药动学。方法12只Beagle犬随机分为复方丹参双相胶囊组、复方丹参双相胶囊老化组、复方丹参胶囊组、复方丹参胶囊老化组,口服给药,于0.25、0.5、0.75、1、2、4、6、8、10、24 h采血,UPLC-MS/MS法测定丹参酮Ⅱ_(A)、丹酚酸B、三七皂苷R_(1)、人参皂苷Rg_(1)、人参皂苷Rb_(1)血药浓度,GC-MS法测定龙脑血药浓度,计算主要药动学参数。结果与复方丹参胶囊组比较,复方丹参双相胶囊组、复方丹参双相胶囊老化组各有效成分AUC_(0~t)、MRT_(0~t)、T_(max)、C_(max)、t_(1/2)无明显变化(P>0.05);复方丹参胶囊老化组各有效成分T_(max)无明显变化(P>0.05),人参皂苷Rg_(1)、龙脑MRT_(0~t)缩短(P<0.05),丹酚酸B、人参皂苷Rg_(1)、龙脑AUC_(0~t)、C_(max)降低(P<0.05)。结论复方丹参双相胶囊中独特的冰片处理方式不会对其他有效成分在Beagle犬体内释药产生不利影响,与复方丹参胶囊相比充分体现出优越性。

AIM To compare the in vivo pharmacokinetics of tanshinone Ⅱ^(A),salvianolic acid B,notoginsenoside R_(1),ginsenoside Rg_(1),ginsenoside Rb_(1) and borneol from Compound Danshen Biphasic Capsules and Compound Danshen Capsules in Beagle dogs.METHODS Twelve Beagle dogs were randomly assigned into Compound Danshen Biphasic Capsules group,aged Compound Danshen Biphasic Capsules group,Compound Danshen Capsules group and aged Compound Danshen Capsules group and given oral administration,after which blood collection was performed at 0.25,0.5,0.75,1,2,4,6,8,10,24 h,UPLC-MS/MS method was adopted in the plasma concentration determination of tanshinone Ⅱ_(A),salvianolic acid B,notoginsenoside R_(1),ginsenoside Rg_(1) and ginsenoside Rb_(1),GC-MS was applied to determining the plasma concentration of borneol,and main pharmacokinetics parameters were calculated.RESULTS Compared with the Compound Danshen Capsules group,the Compound Danshen Biphasic Capsules group and aged Compound Danshen Biphasic Capsules group demonstrated no obvious changes in AUC_(0-t),MRT_(0-t),T_(max),Cmaxand t_(1/2)for various active constituents(P>0.05);the aged Compound Danshen Capsules group displayed no obvious changes in T_(max)for various active constituents(P>0.05),shortened MRT_(0-t)for ginsenoside Rg_(1)and borneol(P<0.05),and decreased AUC_(0-t),C_(max)for salvianolic acid B,ginsenoside Rg_(1)and borneol(P<0.05).CONCLUSION The unique treatment method for Borneolum in Compound Danshen Biphasic Capsules dose not exert adverse influence on in vivo drug release of other active constituents in Beagle dogs,fully reflecting the superiority as compared with Compound Danshen Capsules.