Based On The Number Of Traditional Chinese Medicine, Taking Pd/pk Model Research Model

The research of daily administration times of traditional Chinese medicine is one of the important study content in the usage research of TCM, and it is the key matter related to the safety and efficiency of clinic. However, it was neglected by researchers for a long time, and this field is almost blank. As a result, our group built up a method named "PD/PK" to research the rational daily administration times of TCM, and it was used to study the daily administration times of Rheum when used to purgation and treat jaundice. In this paper, we studied the daily administration times of TCM from single Rheum to compound recipe (Yinchenhao Tang, to be abbreviated as YCHT); furthermore, we applied the integrated pharmacokinetics and serum pharmacology into the PD/PK model use Rheum as the model medicine.Objective:To study the rational daily administration times of YCHT when it is used to treat experimental jaundice in rats based on PD/PK model; to study the rational daily administration times of Rhubarb when it is used to reduce oxidative damage based on the serum pharmacology and integrated pharmacokinetics (SPD/IPK). We anticipated exploring and consummating the research pattern of daily administration times of TCM constantly.Methods:1. Rats were modeled by4%ANIT(75mg/kg, dissoved in olive oil) for48h, then YCHT was drenched to them with a dose of0.324g/kg(extract, calculated with the clinical dosage) once a day,0.162g/kg twice a day and0.108g/kg three times a day, respectively. The total bile and the flow rate of bile were observed after the first administration; blood collected from the orbital sinus after different intervals was used to investigate the levels of liver enzymes (such as ALT, AST) and bilirubin (such as TBIL and DBIL), and determine the concentration of6,7-dimethoxycoumarin (DME) in the blood plasma using HPLC at the same time, then we obtained the time-effect curve and time-dose curve. The rational daily administration times of YCHT when used to treat experimental jaundice was determined based on the comprehend analysis of time-effect and time-concentration relationships.2. Rhubarb extract was drenched to rats3.6g/kg once a day,1.8g/kg twice a day and1.2g/kg three times a day, respectively. Blood collected from the veins behind the eye sockets after different intervals was used to determine the concentration of rheinic acid, aloe-emodin, chrysophanol, physcion, emodin in the blood plasma and the rate of removing superoxide anion in vitro. Calculation the pharmacokinetic parameters of the above components, use the area under the curve of each component (AUC0-8) as a percentage of custom weighting factor to get its integrated pharmacokinetic curve, then conduct correlation analysis with the antioxidant effects, determine the rational daily administration times of rhubarb for the oxidative damage.Results:1. The total bile within10h of the rats which were administered one time a day(G1) was1.65and1.33times higher than that of two and three administrations(G2and G3) a day, respectively, and the four biochemical indexes(TBIL、ALT、DBIL、 AST) of G1decreasing faster than G2and G3(p<0.05). On the other hand, the blood drug level of6,7-dimethoxycoumarin when administrated one time a day could maintain in a higher level for a longer time, and its AUC0�'t were higher than G2and G3(G1>G2>G3), and it coincidence with the results of pharmacodynamics.2. In the experiments of anti-oxidation, the relationship of the AUC of anti-oxidation effect-time was G2>G3>G1, and this result indicated that the anti-oxidation effect was the best when gave Rheum2times a day. The AUC of integrated pharmacokinetics was G2>G3>G1, and there was good correlation between integrated pharmacokinetics rhubarb anthraquinones and the Pharmacodynamics of antioxidant effects in vitro.Conclusions:We could obtain the follow conclusions after synthetical analysis of pharmacokinetics and pharmacodynamics:It is more appropriate to administrate one time a day of YCHT when it was used to treat jaundice but it is more suitable to administrate two times a day of Rheum when it was used as antioxidant.