Effect of Xiongbing compound on the pharmacokinetics and brain targeting of tetramethylpyrazine

Objectives To investigate the effect of the Xiongbing compound (XBC) on the pharmacokinetics and brain targeting of tetramethylpyrazine (TMP). Methods Three microemulsions containing the same TMP concentration were prepared. XBC microemulsions were made from Rhizoma ligustric Chuanxiong extracts, borneol and TMP. TMP microemulsions were made with TMP only. Borneol microemulsions contained borneol and TMP. Microdialysis with high performance liquid chromatography (HPLC) was used to measure the concentration of TMP in the blood and striatum after intravenous (i.v.) or intragastric (i.g.) administration of the three different microemulsions. Key findings The pharmacokinetics of free TMP concentration in the blood and the striatum fit a first‐order rate, open two‐compartment model after intravenous and intragastric microemulsion administration. The maximal concentration (C_max) and area under curve (AUC) values in the XBC microemulsion i.v. group were significantly higher than that in the TMP microemulsion and borneol microemulsion i.v. groups. After XBC microemulsion i.g. administration, the t_1/2, mean residence time (MRT) and AUC of TMP in both plasma and brain tissues were greater than those with TMP microemulsion and borneol microemulsion administration. The relative brain targeting efficiency of TMP for the XBC microemulsion i.v and i.g. groups relative to the TMP microemulsion and borneol microemulsion groups were greater than 1. Conclusion XBC microemulsion can enhance TMP oral bioavailability, brain targeting and tissue distribution, mainly through a synergistic action of Rhizoma ligustric Chuanxiong extracts and borneol.