Pharmacokinetic comparisons of single herb extract of Fufang Danshen preparation with different combinations of its constituent herbs in rats

Abstract

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.