Evaluation of the protective effect of salvianolic acid A on ischemic heart failure by a multi-target pharmacokinetic-pharmacodynamic model / 中国药科大学学报

ABSTRACT

@#The aim of this study was to develop a multi-target pharmacokinetic-pharmacodynamic(PK-PD)model for the evaluation of the protective effect of salvianolic acid A(Sal A)on ischemic heart failure based on a metabolic balance model. The rats were assigned to 3 groups sham-operated group(saline), ischemic heart failure group(saline)and Sal A-treated group(Sal A, 1 mg/(kg ·d), ip). The concentrations of brain natriuretic peptide(BNP), angiotensin II(Ang II), malondialdehyde(MDA), asymmetric dimethylarginine(ADMA)and the activity of glutathione peroxidase(GSH-Px)in rat plasma were determined before and at 1, 2, 3, and 4 weeks after ligation in all the groups. A multi-target PK-PD model was developed based on the change rate of metabolic disruption parameter k and was eventually used to integrally evaluate the protective effect of Sal A on ischemic heart failure. Sal A showed improvement effects on multiple biomarkers and the correlation study demonstrated a good relationship between dynamic parameter k and left ventricular ejection fraction(LVEF). More importantly, the multi-target model well fitted the relationship between AUC and the change rate. The multi-target PK-PD model provides a novel method to integrally evaluate the protective effect of Sal A, which might offer a new strategy for the establishment of a PK-PD model that embodies the characteristics of traditional Chinese medicine.