Pharmacokinetics of Luteolin and Apigenin in Rats after Single Oral Administration of Chrysanthemum morifolium Extract at the Dose of Effectiveness and Approximating to the Maximal Tolerance

OBJECTIVE To evaluate the pharmacokinetics of luteolin and apigenin,the main effective components of Chrysanthemum morifolium extract(CME),and study the relationship between main pharmacokinetic parameters and dosage,under the series dosages of effectiveness and approximate to the maximal tolerance dose of CME by single oral administration to rats.METHODS20 male SD rats were randomly allocated into 4 groups of 5 rats each,and received CME by gavage at the doses of 100,200,400,and 12 000 mg·kg-1,serial plasma samples were collected over 72 h before and after administration.Iuteolin and apigenin were analyzed by modified HPLC method.Pharmacokinetic parameters,including the peak concentrations(ρmax),the areas under the concentration versus time curves(AUC),and the elimination half life(t1/2),the plasma clearance(CL),the apparent volume of distribution(Vd) were evaluated by software DAS(V2.0) with non-compartmental method.RESULTSWithin 100～400 mg·kg-1,as the dose of CME increased in the ratio of 1∶2∶4,the ρmax of luteolin and apigenin increased in the proportion of 1.0∶2.0∶4.1 and 1.0∶2.4∶4.4,the AUC increased in 1.0∶2.1∶4.6 and 1.0∶2.0∶4.3,whereas the other pharmacokinetic parameters did not change significantly among the different dose groups.And of luteolin and apigenin was as follows: t1/2 7.75～8.93 h and 6.51～7.05 h,CL 8.94～11.8 and 1.34～1.69 L·h·kg-1,Vd 43.0～55.2 L·kg-1 and 11.4～13.7 L·kg-1,respectively.However,as the dose increased from 400 to 12 000 mg·kg-1,the ρmax of luteolin and apigenin increased by 2.4 and 2.0 times,and the AUC increased by 6.4 and 3.1 times,respectively,while the t1/2,CL,Vd increased obviously compared with the 400 mg·kg-1 group.CONCLUSIONThe pharmacokinetic characteristics of luteolin and apigenin in rats were linear over the CME dose range of 100-400 mg·kg-1,and nonlinear over the dose range of 400-12 000 mg·kg-1.