Pharmacokinetic-pharmacodynamic(PK-PD) modeling of salvianolic acid A on the plasma homocysteine in rats

Elevated plasma total homocysteine (tHcy) level has been acknowledged as an independent risk factor for cardiovascular diseases.Salvianolic acid A (SalA) is one of the major active water-soluble ingredients of Salvia miltiorrhiza.The pharmacokinetics (PK) and pharmacodynamics (PD) of SalA on plasma tHcy in methionine-loading rats was evaluated.Acute treatment with a single dose of SalA (1,2.5,5 mg/kg) in rats with Met loading significantly reduced the plasma tHcy level in a dose-dependent manner.In order to characterize the effect of SalA on plasma tHcy，a mechanism-based PK-PD model was developed.Modeling and simulations well fitted the measured values.By comparison with the PK-PD model of danshensu(DSS)，it was found that the elevated effect of SalA on tHcy by methylation was weaker than that of DSS,while trans-sulfuration promotion effect of SalA on tHcy was greater than that of DSS.