ABSTRACT
Objective To study the rational daily administration times of Yinchenhao Decoction (YCHD) when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.MethodsRats were modeled by 4％ 1-naphthylisothiocyanate (75 mg/kg) for 48 h,then YCHD was drenched with doses of 0.324 g/kg (extract,calculated with the clinical dosage) once,0.162 g/kg twice,and 0.108 g/kg thrice a day,respectively.The total bile and the flow rate of bile were observed after the first administration; Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes (ALT and AST) and bilimbins (TBIL and DBIL),and determine the concentration of 6,7-dimethoxycoumarin (DME) in the plasma using UPLC at the same time,then we obtained the time-effect and time-dose curves.The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships.ResultsWithin 10 h the total bile of rats which were administered once daily (G1) was I.65 and 1.33 times higher than that of twice and thrice (G2 and G3) a day,respectively,and the four biochemical indexes (TBIL,ALT,DBIL,and AST) of Gl decreased faster than those of G2 and G3 (P ＜ 0.05).On the other hand,the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time,and its Cmax and AUC0→t were higher than those of G2 and G3,which might be the main reason why its effect was the most significant.ConclusionIt is more appropriate to administrate once daily when YCHD is used to treat jaundice.
ABSTRACT
<p><b>OBJECTIVE</b>To study the rational daily administration times of rhubarb when it is used to treat experimental jaundice in rats, at the same time, validate the accuracy and feasibility of the method which was previously established to research the rational daily administration times of rhubarb (PD-PK method), and consummate it.</p><p><b>METHOD</b>After the rats were modeled by 4% ANIT (75 mg x kg(-1)) for two days, rhubarb extraction was drenched 3.6 g x kg(-1) once a day, 1.8 g x kg(-1) twice a day and 1.2 g x kg(-1) three times a day, respectively. Then the total bile and the flow rate of bile were observed. Blood was collected from the veins behind the eye sockets after different intervals and was used to investigate the biochemical indexes of the blood serum, such as TBIL, ALT, ALP, AST and GGT, and to determine the concentration of rheic acid in the blood plasma, then the time-effect curve and time-dose curve were obtained. The rational daily administration times of rhubarb was determined when it was used to treat experimental jaundice based on the comprehend analysis of time-effect and time-concentration relationships.</p><p><b>RESULT</b>Compared with the groups which were administered once a day and three times a day, the total bile within 8 h of the rats which were administered twice a day was 1.56 and 1.7 times higher, respectively, while the TBIL was 23%, 22%, and ALT was 86%, 65% of the other two, ALP was 50%, 71% of the other two, respectively. With administrated twice a day, the blood concentration of rheic acid could maintain a high level for a longer time, which maybe the main reason for its effect.</p><p><b>CONCLUSION</b>The method based on pharmacodynamics and pharmacokinetics is scientific and feasible to study the rational daily administration times of traditional Chinese medicine. Rhubarb is better to administrate two times a day to treat jaundice.</p>
Subject(s)
Animals , Female , Male , Rats , Alkaline Phosphatase , Blood , Bile , Jaundice , Drug Therapy , Plant Extracts , Pharmacokinetics , Therapeutic Uses , Rats, Wistar , RheumABSTRACT
To compare the microcalorimetric fingerprint profiles of Lonicerae japonicae Flos (Lj.F) and Lonicerae Flos (L.F), microcalormietry was applied to find the heat change regularity of Bacillus shigae (B. shigae) metabolism affected by Lj.F and L.F (we choose Lonicera macranthoides Hand.-Mazz in this paper) with different concentrations. The thermogenic curves and thermodynamics parameters were investigated as evaluation index, and then the date of experiment was studied by similarity analysis. All the results indicated that the Lj.F and Lonicera macranthoides Hand.-Mazz (L.m.H-M) significantly impacted the microbial growth and had good similarity in its inhibitory activities. The combination approach of chemical analysis with bioassay was developed and employed to ensure the safety and efficacy of Chinese herbal medicines.