Antagonism activity against acute myocardial ischemia of Paeoniflorin and its pharmacokinetic/pharmacodynamic (PK/PD) modeling in rats

The aim of the present work was to investigate the effects of paeoniflorin (PF) on acute myocardial ischemia in rats. Meanwhile, after intravenous and oral administration of PF, the pharmacokinetic and pharmacodynamic characters of PF in rats were also studied. Plasma concentration of paeoniflorin was determined using a simple and rapid HPLC method. Nonlinear mixed-effect modeling (NONMEM) method was used for pharmacokinetic (PK) and pharmacodynamic (PD) analysis. A two-compartment model with first-order degradation in the absorption compartment was employed for the PK data analysis. The results showed that PF exhibited significant antagonism against acute myocardial ischemia and a PK/PD link model and two IDR models were developed and compared for anticoagulant activity of PF. It was concluded that the integrated PK/PD model could well characterize PK and PD behaviors of PF in rats.