Studies on Brain Pharmacokinetics of Xiongbing Microemulsion by Microdialysis Technique in Awake and Freely-moving Rats

Objective To investigate the brain pharmacokinetics of tetramethylpyrazine(TMP) in Xiongbing Microemulsion after intragastric(i.g.),intravenous(i.v.) and intranasal(i.n.) administration.Methods Striatum dialysate samples were continuously collected by brain microdialysis technique in awake and freely-moving rats after the three routs of administration.The concentration of TMP in dialysate samples were measured by HPLC.The pharmacokinetic parameters were calculated by pharmacokinetic software DAS2.1.Results All of the measured pharmacokinetics of free cerebral TMP concentration fitted single-compartment model after i.g.,i.v.and i.n.administration.The MRT0-∞,was 73.7,38.8,70.6 min,Tmax was 15,5,15 min,Cmax was 249.2,2579.3,1175.1 μg·L-1,and AUC0-∞ was 19806.9,106410.7,62973.3 μg·min·L-1,respectively.The local bioavailability of TMP in the brain was 59.2 % after i.n.administration,and 18.6 % after i.g.administration.Conclusion The bioavailability of Xiongbing Microemulsion is quite low after i.g.administration.On the contrary,Xiongbing microemulsion has the greatest bioavailability after i.v.administration,and TMP can be absorbed into the brain rapidly and then goes into rapid metabolism,which results in the short residence time in the brain.Xiongbing microemulsion has higher bioavailability after i.n administration,and the mean residence time in the brain is longer,which shows certain value for further research of Xiongbing Microemulsion by i.v.administration.