[Synergistic Effects of Clopidogrel and Xuesaitong Dispersible Tablet by Modulating Plasma Protein Binding]

The ginsenoside Rb1,which account for platelet aggregation of Xuesaitong dispersible tablet, was selected to investigate the synergistic effects of clopidogrel( CPG) and Xuesaitong dispersible tablet drug by modulating plasma protein binding rate aspect.

The HPLC and equilibrium dialysis were employed to determine the concentration of Rb1 both in dialysate( PBS) and blank plasma from healthy volunteer blood donors. The differences in protein-binding rate between Xuesaitong dispersible tablet alone( the concentration of ginsenoside Rb1 were 5. 0,1. 0,0. 4 μg / m L,respectively) and combined with CPG( each add CPG 2 μg / m L) were then compared. The three-dimensional spatial structure of the blank plasma albumin( HSA) in the subjects was construct by rabbit plasma albumin( PDB ID 3V09) template and evaluated by PRO-CHECK and ERRAT methods. Molecular simulation technique was used to display the competition mechanism with human plasma protein.

The protein binding rate of Xuesaitong dispersible tablet alone group in plasma PBS and human plasma at high( the concentration of ginsenoside Rb1 were 5. 0 μg / m L),middle( the concentred of ginsenoside Rb1 were 1. 0 μg / m L) and low( the concentration of ginsenoside Rb1 were 0. 4 μg / m L) concentrations were( 58. 17 ±3. 82) %,( 57. 43 ± 3. 21) %,( 55. 63 ± 3. 42) % respectively. When combined with CPG( each add CPG 2 μg / m L),the protein binding rate value were decline to( 46. 54 ± 3. 35) %,( 49. 25 ± 3. 56) %,( 48. 15 ± 3. 76) %,respectively. The molecular simulation results suggested that the two compounds have competitive synergistic effects with human plasma protein.

The present investigation suggestes that there are synergistic effects of CPG and Xuesaitong dispersible tablet by modulating plasma protein binding rate of ginsenoside Rb1.