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(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. 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.

[The pharmacokinetics study on Sinomenine transdermal patch on anaesthetized Beagle dogs].

OBJECTIVE: To explore the pharmacokinetic of Sinomenine transdermal patch. METHODS: The plasma drug concentration of Beagle dogs was determined after administration with HPLC-UVD as analysis tools. The pharmacokinetics parameters were fitted with kinetica software package. RESULTS: The exclusive analysis method was established with the following pharmacokinetics parameters: T (peak) = 8 h, Cmax = 366 ng/mL, MRT = 13 h. The pharmacokinetic characteristics was accordance with one-order rate and two-compartment model. CONCLUSION: The method is preferable to be applied to the pharmacokinetics research and further applied pharmacological study which will play a reference role in clinical application.

[Bioequivalence study of sinomenine patch by microdialysis].

OBJECTIVE: To study bioequivalence of Sinomenine patch made by different preparation process, and to testify feasibility and superiority of microdialysis as a new method in topical bioequivalence study. METHOD: Normal gel patch and liposome gel patch of sinomenine were prepared by different preparation, nude mouse served as the experimental subjects sampling method of drug in the skin was tissue homogenization microdialysis, and drug concentration in dialysate was determined by HPLC. RESULT: Results of tissue homogenization showed that liposome gel patch leads more remainder drug in the skin of nude mouse than normal gel patch, and results of microdialysis showed that liposome gel patch led higher instantaneous drug concentration than normal gel patch. Concentration-time curve of sinomenine in the skin accorded with the results of most dermal delivery systems studies over the world. CONCLUSION: Topical bioequivalence of liposome gel patch of sinomenine is higher than that of normal gel patch of sinomenine. Microdialysis can be used to study bioavailability and bioequivalence of different preparation.

[Determination in vitro of rat plasma protein binding rate of sinomenine by using microdialysis method].

AIM: To determine in vitro the rat plasma protein binding rate by using microdialysis method. METHODS: The binding rate was determined by using microdialysis probe as sampling tools and zero-net flux method as calibrating method. The regression equation was made by the difference of concentrations between the dialysis sample and the perfusate. The x-intercept of regression equation was the free drug concentration (Cf). The plasma protein binding rate was calculated by using the following equation: f = ( C0 - Cf)/C0. RESULT: The binding rate was kept relatively stable in the studied concentration range. CONCLUSION: It is feasible that the plasma protein binding rate can be determined by using microdialysis method.

[Study on determination of entrapment efficiency of sinomenine liposomes].

OBJECTIVE: To establish an HPLC method for the determination of entrapment efficiency of sinomenine liposomes. METHOD: The liposomes and dissociated drugs were separated by sephadex filtration, mini-column centrifugation and dialysis. The methodology study and the optimization of determining condition were carried out at the same time. RESULT: Sephadex filtration could effectively separate the sinomenine liposomes from dissociated sinomenine. The column recovery was 98.8%, the average entrapment efficiency of three tests was64.9%, RSD 2.67%. CONCLUSION: The method was simple, exact, and had a good reappearance. It can be used to examine the entrapment efficiency of sinomenine liposomes.

[A study on the percutaneous penetration of artesunate from various reservoir vehicles].

OBJECTIVE: To determine the main factors which affect the percutaneous penetration of artesunate and provide efficient data for the artesunate transdermal delivery system. METHOD: Transdermal speed constant and accumulative amount of 12 hours were used for the estimations of various reservior vehicles, and the supplement orthodox design was used to study the effect of pH, various proportion of IPA/Water/IPM, and drug concentration. RESULT: Drug concentration and pH were the main factors which affected the percutaneous penetration of artesunate. CONCLUSION: The suitable reservior vehicle can prompt the percutaneous penetration of artesunate, and artesunate TTS will be made with further studies.