Pharmacokinetic comparative study of GAS with different concentration of tetramethylpyrazine and ferulic acid on liver-yang hyperactivity migraine model by blood-brain microdialysis method.

Abstract Gastrodia elata and Ligusticum chuanxiong are used to treat primary headaches for many years. Gastrodin (GAS) and tetramethylpyrazine (TMP)/ferulic acid (FA) are the main active ingredients of Gastrodia elata and Ligusticum chuanxiong, respectively. Previous studies demonstrated the pharmacokinetics of GAS, TMP, and FA in the blood and brain interstitial fluids (BIF) in healthy animals but not in animal model with liver–yang hyperactivity migraine. Hence, this study examined the pharmacokinetics of GAS after its oral administration in the presence of different concentrations of TMP and FA in animals with liver–yang migraine hyperactivity. In the control group, GAS was administrated without TMP and FA. Pharmacokinetic parameters were determined using the blood-brain microdialysis in combination with the high-performance liquid chromatography method. Results revealed that the maximum drug concentrations (Cmax) in the serum, area under curve (AUC), and mean residence time (MRT) of GAS decreased in normal animals, whereas Cmax increased significantly in model animals. These findings indicate that varying concentrations of TMP and FA play an important role in the pharmacokinetics of GAS in both normal and migraine model animals, validating the utility of the ancient formulation.