Pharmacokinetics Study On Different Compatibilities Of Wujiwan Prescription Extracts

Purpose of research:Aim to investigate the compatibility principle of Wujiwan extracts, pharmacokinetics (PK) method was employed to investigate the compatibility of active ingredients of Wujiwan prescription. We studied the effects of different compatibilities on the physiological disposition of the five active ingredients :berberine&palmatine, evodiamine&rutaecarpine, paeoniflorin in vivo. By analyzing the contribution degree of drugs to the whole prescription and determining the best compatibility of whole prescription,we discussed the rationality of the compatibility.Methods and results:1 .Preparation of Wujiwan prescription extractsOrthogonal design was adopted to optimize the extraction methods from the effective components of the Chinese herbal medicine in Wujiwan, indicated by the extraction of berberine&palmatine,evodiamine&rutaecarpine,paeoniflorin.The effective components have been extracted and demonstrated that the prescription was in agreement with Chinese Pharmacopeia (2005．1^st part), a standard publication of Wujiwan.2．Pharmacokinetics studies on individual drugs of WujiwanThe method of plasma concentration for detecting the five ingredients after oral administration extracts of Wujiwan in Rats was established respectively by LC-MS,and it was applied for the pharmacokinetics studies of the five ingredients.The experimental results was showed below: the kinetic process of berberine&palmatine in Rats in vivo was fitted to a one-compartment model at low dosage,while it was fitted to two-compartment model at middle and high dosages; the kinetic process of evodiamine&rutaecarpine in Rats in vivo was fitted to a one-compartment model; the kinetic process of paeoniflorin in Rats in vivo was fitted to a one-compartment model.For oral administration, the pharmacokinetic parameters(AUC&Cmax) of five ingredients have good linearity among the dosages, MRT(except evodiamine&rutaecarpine) also presented increasing in vivo.it indicates the the kinetic process of five ingredients were all according to the linear dynamics in vivo.3．Pharmacokinetics studies on different compatibilities of Wujiwan extractsL₉(3⁴) orthogonal design was adopted to construct the different compatibilty prescirptions of Wujiwan extracts.The method of simultaneous detection for berberine &palmatine, evodiamine&rutaecarpine, paeoniflorin in Rats in vivo was established by LC-MS,and it was used for the pharmacokinetics studies of different compatibiltyprescriptions.As a conclusion,there are significant difference on the PK parameters between the different compatibilities of berberine,palmatin,evodiamine,rutaecarpine,paeoniflorin.The concentration-time data of same compound was not only fitted to one-compartment model,but also fitted to two-compartment model in different compatiblities after oral administration.The PK parameters of each ingredient,such as AUC,Cmax(except berberine)&MRT were higher in compound prescripitions than individual drugs in general.and for Tmax&Ka presented different changing characteristics.All of these indicate that the compounds have more residence time in vivo in compound prescripitions ,and bring into full play to pharmacodynamic effect.It suggests that the principals of compatiblity have certain values and material base.Based on the work mentioned above,we took the mathematics methods to analyze the PK parameters,such as bivariate correlation analysis,regression analysis, weighted method of normalization, then we drew the relativity between drugs and PK parameters and the contribution to the whole prescription..Combined with the compatibliy theory of traditional Chinese medicine compound prescriptions.the compatibility rationality of Wujiwan prescription was annotated.To sum up, preliminary research has been conducted on the compatiblityt of Wujiwan by the method of PK in this dissertation.The dynamic change of compounds was quantitative analyzed in differen compatiblities,and the compatiblity law of traditional Chinese medicine compound prescriptions was explained in some extent.thus,we conclude the optimizing compatibility being Huanglian:Zhiwuzhuyu: Chaobaishao=6:3:6 by comprehensive analysis.