Study On Absorption Characteristics And Pharmacokinetics Of Xin Shao Composing Prescriptions

Objective To develop the methods of Caco-2 cells model and pharmacokinetics(PK) parameters.And the aim of this study was to simultaneous evaluate the absorption components,absorption mechanism,influence factors and pharmacokinetic characteristicss,of the main components in XinShao extract.Study on the change of compatibility pre-and post cell intake amount and pharmacokinetics parameters,in order to investigate XinShao composing prescriptions compatible rationality and scientific.Methods In Vitro use Caco-2 cells uptake model and a sensitive ultra performance liquid chromatography electrospray ionization tandem mass sepctrometry (UPLC-ESI-MS/MS) method for analyzing nine components of Chlorogenic Acid,Caffeic acid,3,4-dicaffeoylquinic acid,4,5-dicaffeoylquinic acid,scutellarin,apigenin-7-O-glucronide,paeoniflorin,albiflorin,gallic acid in cell lysis buffer and in plasma,and the mechanism of the nine componds absorption in cells was explored by studying the various time,pH,temperature and inhibitors on the uptake of XinShao extract in cells.And study on different drug concentration of XinShao unilateral and composing prescriptions absorption in cells,and the Comparison with compatibility pre-and post Caco-2 cell intake amount.Rats were given a single doses by intravenous administration and injection XinShao extract in vivo, and measured blood plasma concentration at different time,to investigating the changes of the compatibility pre-and post of pharmacokinetic porameters.Results The method were in accord with technical principle promulgated.Results of cell uptake experiment:XinShao extract in Caco-2 cells uptake was time,concentrations,temperature dependent.different concentration concentrations of eight components in various intestinal sections were the linear absorption (r2>0.9),consistent with passive diffusion process.The cell intake amount of Caffeic acid and scutellarin were decreased along with uptake time,the cell intake amount of paeoniflorin decreased along with pH,but Caffeic acid was increased along with pH.The up takes of Caffeic acid and scutellarin in Caco-2 cells were increased by p-gp inhibitors significantly,and Caffeic acid and scutellarin were the substrates of P-gp.The drug intake amount of XinShao composing prescriptions were significantly higer than unilateral(P<0.05).The results of PK showed the five components appear in plasma very fast after intravenous administration to rat. Tmax were 0.67～10.33 h, MRTo-t were 5.36～13.35 h, AUC(o-t) were 17.87～56.00 mg/mL*h, t/2z were 4.29-17.03 h.After a single intravenous injection XinShao composing prescriptions and unilateral extract to rat,The change of pharmacokinetics parameters of compatibility pre-and post experiment:The composing prescriptions of Caffeic acid and scutellarin AUC(0-t)were significantly higer than unilateral(P<0.05).but it other pharmacokinetics parameters and other six components pharmacokinetics parameters were increased,respectively.The Caffeic Acid,paeoniflorin,albiflorin,gallic acid,scutellarin absolute bioavailability for oral use were 317.13%、11.61%、2.40%、 36.48%,27.44%.Conclusion This experiments has been developed and validated a sensitivity ultra performance liquid chromatograp-by electrospray ionization-tandem mass sepctrometry (UPLC-ESI-MS/MS) method for analyzing the concentration of XinShao extract in biological samples.The work lays a scientific foundation for further understanding the absorption mechanism,influence factors of the nine components in XinShao extract,Study on the change of compatibility pre-and post cell intake amount and pharmacokinetics parameters,and obtain the five components pharmacokinetics parameters and the absolute bioavailability.Also provides a theoretical and experimental foundation for rationality and scientific,and drug development of the XinShao composing prescriptions.