Pharmacokinetic-pharmacodynamic evaluation of the major component astragaloside IV on the immunomodulatory effects of Yu-ping-feng prescription.

Yu-ping-feng decoction (YPF), a traditional Chinese medicine (TCM) prescription, is widely used to treat some respiratory tract diseases. This study was aimed to set up a pharmacokinetic-pharmacodynamic (PK-PD) model to assess dose-effect relationships for immunomodulatory effects of YPF in rats and to clarify compatibility mechanisms for TCM prescription system. Serum samples taken after YPF administration were tested on spleen cells of rats in vitro and proliferation ratio of spleen cells was used as end points to evaluate pharmacodynamic properties of immunoregulatory effects of YPF prescription. And with a HPLC-MS method, concentrations of Astragaloside IV (AS), a main component of YPF, were determined to achieve pharmacokinetic parameters after administration of a simplified prescription which is composed with AS, Atractylenolide I and Prim-O-glucosylcimifugin which are representative components of YPF. A plot of serum AS concentrations versus time and effects showed that there was a correlated relationship between AS concentrations and effects of YPF, and the concentration-response curve which was based on an E max model showed a counterclockwise hysteresis manner. A PK-PD model with Sheiner's method was used to describe time course of AS concentration in blood compartment and effect compartment, and main parameters with the PK-PD model were calculated. These results showed that there is a symmetry relationship between serum AS concentrations and responses of serum containing medicine of YPF prescription, which means that AS plays an important role in immunoregulatory effects of YPF. And the investigation on dose-effect relationships has displayed a feasible method to clarify mechanisms of combination for TCM prescriptions.