The Pharmacokinetics Study Of Multicomponent Drug Based On Metabolomics

Objective Two approaches were applied to investigate the metabolism characteristics of multicomponent drug Huangqi Decoction(HQD),hoping to provide new insights to the pharmacokinetics(PK)and pharmacodynamics research of HQD and to validate the feasibility and effectiveness of the new Ploy-PK strategy on the pharmacokinetics study of multicomponent drugs.Methods Two approaches,the traditional metabolomics combined with Poly-PK strategy and the traditional pharmacokinetics,were applied to examine the alterations of plasma metabolic profiles and kinetics performances of multiple drug components comparing pre and post dose(multiple time-points)of HQD in healthy volunteers.Two analytical platforms,ultra performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-QTOFMS)and gas chromatography time of flight mass spectrometry(GC-TOFMS),and diverse differential and association analysis methods were used.Results As results from traditional metabolomics and Poly-PK strategy shown,485 compounds were significantly altered after intake of HQD,including 57 absorbed HQD metabolites,293 metabolites of the absorbed HQD and 165 endogenous metabolites.The typical PK parameters acquired from Poly-PK strategy and traditional PK approach were consistent.Conclusions This research applied Poly-PK strategy successfully to the study of pharmacokinetics of multicomponent drug HQD,for the first time.The new Poly-PK strategy has prominent advantages on pharmacokinetics and pharmacodynamics evaluation with more accurate and broader information on the effect of HQD on human metabolism,comparing with traditional PK approach.It is worthy of popularization and application.