Rational Daily Administration Times of Yinchenhao Decoctionin Rats with Jaundice Based on PD/PK

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.Methods Rats 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 bilirubins (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.Results Within 10 h the total bile of rats which were administered once daily(G1) was 1.65 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 G1 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.Conclusion It is more appropriate to administrate once daily when YCHD is used to treat jaundice.