Pharmacokinetic-pharmacodynamic modeling analysis for hydroxysafflor yellow A-calycosin in compatibility in normal and cerebral ischemic rats: A comparative study

Astragalus and Safflower are commonly used in the treatment of stroke. Studies have shown that their two active components, hydroxysafflor yellow A (HSYA) and calycosin (CA), have protective effects on cerebral ischemia-reperfusion injury (I/R). However, the pharmacokinetic-pharmacodynamic (PK-PD) modeling study of the combination of the two components has not been reported in rats. The study aimed to perform combined PK-PD modeling of HSYA and CA in normal and cerebral ischemia model rats to explain quantitatively their time-concentration-effect relationship. To make the middle cerebral artery occlusion (MCAO) model. SD rats were randomly divided into normal treated group (NTG) (n = 6), model group (MDG) (n = 6) and model treated group (MTG) (n = 6). Plasma was collected from the mandibular vein after 0, 2, 5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 180, and 240 min after intravenous administration. Rats in NTG and MTG were administered the same dose of HSYA (5 mg/kg) and CA (8 mg/kg) by tail vein injection. HPLC-VWD method was used for detection and analysis. Simultaneously, ELISA was performed to detect the levels of IL-1β and caspase-9 in rat plasma at different time points. The improvement in the above indicators was compared after administration. Lastly, after combining the pharmacokinetic parameters and pharmacodynamic indicators in vivo, DAS 3.2.6 software was used to fit the PK-PD model. The MCAO model was successfully established. Compared to NTG, there was a significant difference (P