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


RESULTS
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(½), 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.


CONCLUSIONS
XBC microemulsion can enhance TMP oral bioavailability, brain targeting and tissue distribution, mainly through a synergistic action of Rhizoma ligustric Chuanxiong extracts and borneol.
Department of Pharmacy, College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China. wlis68@126.com
Li-Sheng
LS
Wang
Zong-Feng
ZF
Shi
Ying-Feng
YF
Zhang
Qi
Q
Guo
Yu-Wei
YW
Huang
Li-Ling
LL
Zhou
D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism; D001892:Camphanes / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004655:Emulsions; D006207:Half-Life; D041743:Herb-Drug Interactions; D008297:Male; D017551:Microdialysis; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
D001892:Camphanes; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D004655:Emulsions; D011719:Pyrazines; D014665:Vasodilator Agents; C534193:chuanxiong rhizome preparation; C022871:isoborneol; C017953:tetramethylpyrazine