Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
J Pharm Biomed Anal. 2012 Aug-Sep;67-68:77-85. doi: 10.1016/j.jpba.2012.03.058. Epub 2012 Apr 10.
Salvianolic acid B (SAB), tanshinone IIA (TS), ginsenoside Rb₁ (Rb₁), ginsenoside Rg₁ (Rg₁) and notoginsenoside R₁ (R₁) are major active ingredients of Fufang Danshen preparation (FDP) for its protective effects on myocardial ischemia. This study investigated the pharmacokinetics of marker compounds after oral administration of single herb extract and different combinations of constitutional herbs in FDP, and explored potential herb-herb interactions among the ingredients in the multi-herb medicine. The pharmacokinetics study on the target compounds in rat plasma was performed using an optimal ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) coupled with protein precipitation method. There were no statistically significant differences in pharmacokinetic parameters of SAB, TS, Rb₁, Rg₁ and R₁ between single Radix Salvia miltiorrhiza (S. miltiorrhiza) or Radix Panax notoginsen (P. notoginseng) extract and combination treatment. While, in comparison with oral administration of P. notoginseng extract alone, the pharmacokinetic parameters (C(max), AUC(0-72 h), AUC(0-∞), Cl, V), particularly for Rb₁ and Rg₁, were significantly different after oral administration P. notoginseng extract with addition of borneol (p<0.05). The AUC(0-72 h) values of Rb₁ and Rg₁ were significantly increased 1.3-fold and 1.6-fold, respectively, after P. Notoginsen extract co-administered with borneol. The results showed that herb-herb interactions may be accounting for the different pharmacokinetic behaviors of active constituents administered in compound prescriptions versus in single-herb extracts, however, which were not significant in most cases.
丹酚酸 B（SAB）、丹参酮 IIA（TS）、人参皂苷 Rb₁（Rb₁）、人参皂苷 Rg₁（Rg₁）和三七皂苷 R₁（R₁）是复方丹参制剂（FDP）保护心肌缺血的主要活性成分。本研究考察了单味药提取物及 FDP 中君臣药组合给药后标记化合物的药代动力学特征，探讨了多味药中成分之间的潜在的药-药相互作用。采用优化的超高效液相色谱-电喷雾串联质谱法（UPLC-ESI-MS/MS）结合蛋白沉淀法进行大鼠血浆中目标化合物的药代动力学研究。单味丹参或三七提取物与联合用药在 SAB、TS、Rb₁、Rg₁ 和 R₁ 的药代动力学参数方面无统计学差异。与单独口服三七提取物相比，口服加用冰片的三七提取物后，Rb₁ 和 Rg₁ 的药代动力学参数（Cmax、AUC（0-72 h）、AUC（0-∞）、Cl、V），特别是 Cmax 和 AUC（0-72 h），均有显著差异（p<0.05）。加用冰片后，三七提取物中 Rb₁ 和 Rg₁ 的 AUC（0-72 h）值分别显著增加 1.3 倍和 1.6 倍。结果表明，药-药相互作用可能是复方制剂与单味药提取物给药后活性成分药代动力学行为不同的原因，但在大多数情况下并不显著。
