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

Salvianolic acid B (SAB), tanshinone HA (TS), ginsenoside Rb-1 (Rb-1), ginsenoside Rg(1) (Rg(1)) and notoginsenoside R-1 (R-1) are major active ingredients of Fufang Danshen preparation (FOP) 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 FOP, 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, Rb-1, Rg(1) and R-1 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(0-72h), AUC(0-infinity), Cl, V), particularly for Rb-1 and Rg(1), were significantly different after oral administration P. notoginseng extract with addition of borneol (p < 0.05). The AUC(0-72h) values of Rb-1 and Rg(1) 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. (C) 2012 Elsevier B.V. All rights reserved.