Pharmacokinetic Studies Of Biqi Capsule Based On The Theory Of TCM Compatibility

Pharmacokinetic (PK) studies on complex prescriptions of traditional Chinese medicines (TCMs) play an important role in the course of TCM modernization. As an effective proved recipe inherited from the celebrated ancient Chinese doctor Huatuo, Biqi capsule has been frequently and clinically used to treat rheumatoid arthritis and related diseases. Although there were published reports about chemical and pharmacological researches of Biqi capsule, less was known on its pharmacokinetic development. In this dissertation, guided by the theory of TCM compatibility, pharmacokinetic studies were carried out to investigate the PK characteristics of Biqi capsule. And the results were as follows:1. An LC-ESI-MS method has been established for simultaneous determination of strychnine and brucine in biological matrix for the first time. The method was demonstrated to be highly sensitive and selective, with a simple and rapid procedure for sample preparation. It was reliable and suitable for PK studies of the two effective strychnos alkaloids.2. Comparative pharmacokinetic studies were undertaken by orally administered pure strychnine, pure brucine, the king drug, and the whole recipe of Biqi capsule to Wistar rats respectively, with the same single dose. It was found for the first time that compared with the treatments of monomers and the king drug, which showed no significant statistical differences in the pharmacokinetic parameters of strychnine and brucine, Biqi capsule significantly increased the tmax, decreased the Cmaxs by half, and prolonged the mean residence time, but with almost unchanged AUCs. The results indicated that ingredients from Biqi capsule, except the king drug, affected the pharmacokinetic process of strychnine and brucine mainly through delay of absorption.3. On the basis of the theory of TCM compatibility, pharmacokinetic differences were investigated by oral administration of the combination of the minister, assistant and guide drugs of Biqi capsule with the king drug, respectively, to Wistar rats. Both the minister drug and the assistant drug could significantly increase the tmax of strychnine and brucine. But the single herbs from the minister and assistant drugs did not have pharmacokinetic effects on the king drug. The results demonstrated the minister, assistant and guide drugs of Biqi capsule indeed delayed absorption of the king drug, only through reasonable compatibility into the whole recipe.4. Absorption studies were undertaken in the rat everted sacs by treated with pure strychnine, pure brucine, the king drug and Biqi capsule, respectively. Strychnine and brucine could be absorbed into various regions of rat intestines, and the absorption was a first order rate process. The absorption of strychnine and brucine was also linear, with jejunum the main site of absorption. In terms of absorption of strychnine and brucine in rat everted jejunum sacs, the group of Biqi capsule showed significantly less absorption rate and accumulative amount of absorption than the groups of monomer and the king drug. Strychnine and brucine were not substrates of P-glycoprotein. Biqi capsule was found for the first time to have effects on strychnine and brucine in the view of intestinal absorption, which verified the pharmacokinetic results in rats.5. At the same single oral dose of pure strychnine, Biqi capsule significantly increased the tmax, decreased the Cmax of strychnine in rat brain, with almost the same AUC. While there were no significant differences between the brain/blood ratios of strychnine in concentrations at different time intervals and pharmacokinetic parameters. The results showed that through prescription compatibility, Biqi capsule was more protective to central nervous system by reducing toxicity, which was due to absorption delay of strychnine into rat plasma.