Effect of puerarin in Longmaining formula on pharmacokinetics-pharmacodynamics correlation in rats with myocardial ischemia / 中国中药杂志

ABSTRACT

To study the pharmacokinetics of puerarin in compound Longmaining(FFLMN) in normal rats and myocardial ischemia rats, and investigate its correlation with anti-myocardial ischemia effect of FFLMN. Models of myocardial ischemia rats were produced by subcutaneous injection of isoproterenol(ISO), then FFLMN extract solution was administered by gavage. Orbital sinus blood sampling was collected at different time points after gavage. HPLC-UV method was applied to determine the concentration of puerarin in plasma, and compare the difference in pharmacokinetics between normal rats and model rats after application of same dose of FFLMN. Meanwhile, microplate reader was used to determine IL-6 and SOD activities in plasma of different time points, and draw dose-effect curve. The results indicated that the pharmacokinetics of puerarin conformed to the two-compartment model in both normal group and myocardial ischemia model group. In the comparison of main pharmacokinetic parameters between two groups AUC0-∞=(11.451±3.228) mg•h•L⁻¹,AUC0-t=(14.047±3.765) mg•h•L⁻¹, Cmax=(5.623±1.40) mg•L⁻¹ in normal group; AUC0-∞=(68.849±50.396 9) mg•h•L⁻¹, AUC0-t= (58.312±45.802) mg•h•L⁻¹,Cmax=(18.456±7.517) mg•L⁻¹ in treatment group. The SOD level was significantly increased and IL-6 concentration was significantly decreased in plasma, indicating that as compared with the normal group, puerarin in FFLMN had a higher plasma concentration, slower elimination rate and higher bioavailability. Therefore, puerarin concentration in plasma has correlation with the anti-myocardial ischemia effect of FFLMN, which could increase SOD level and inhibit the release of IL-6.