Study on PK-PD combination of ligustrazine in cerebral ischemia reperfusion rats after ig administration of effective parts in compatibility of Chuanxiong Rhizoma and Astragali Radix / 中草药

ABSTRACT

Objective: To research the pharmacokinetic-pharmacodynamic (PK-PD) model of ligustrazine in cerebral ischemia reperfusion (I/R) rats. Methods: To build the middle cerebral artery embolization (MCAO) model. The blood 0.5 mL was collected from orbital venous plexus at 0.083, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, and 6.0 h time points after ig administration of effective parts in compatibility prescription of Chuanxiong Rhizoma and Astragali Radix. The concentration of ligustrazine in serum was determined by RP-HPLC, and then the concentration-time curves were drawn. Meanwhile, the activities of LDH in serum were determined with ELISA Kit. PK-PD modeling was fitted with DAS 3.2.6 software. The PK-PD model parameters were calculated. Results: The effect of ligustrazine on inducing LDH release did not relate directly with the concentration but lagged behind the concentration of ligustrazine in serum. The relationship between effect and serum concentration fits Emax model. Conclusion: This study successfully establishes the combined PK-PD model of ligustrazine after ig administration of different combinations of the active parts in Chinese materia medica (CMM) to rats. This research can be effectively applied to predict PK- PD studies on the main effective components in other compatibility of CMM.