GONG Zi-peng, HU Jian-chun, LI Mei, et al. Establishment of PK-PD Binding Model of Scutellarin and Paeoniflorin in Xinshao Formula Based on Model of Cerebral Ischemia Reperfusion Injury in Rats[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(1): 74-78.
DOI:
GONG Zi-peng, HU Jian-chun, LI Mei, et al. Establishment of PK-PD Binding Model of Scutellarin and Paeoniflorin in Xinshao Formula Based on Model of Cerebral Ischemia Reperfusion Injury in Rats[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(1): 74-78. DOI: 10.13422/j.cnki.syfjx.2018010074.
Establishment of PK-PD Binding Model of Scutellarin and Paeoniflorin in Xinshao Formula Based on Model of Cerebral Ischemia Reperfusion Injury in Rats
Objective:To establish the pharmacokinetic-pharmacodynamic(PK-PD) binding model of scutellarin and paeoniflorin in Xinshao formula. Method:In order to get the drug-time curves of scutellarin and paeoniflorin from Xinshao formula in plasma collected from different time points of a disease model animal
whose concentrations were determined by UPLC-MS/MS.At the same time
two kinds of indexes[superoxide dismutase(SOD) and lactate dehydrogenase(LDH)] in the plasma samples of different time points were determined by the kit for time-effect curves.Then WinNonlin 6.4 software was used to fit the pharmacokinetic parameters of scutellarin and paeoniflorin with compartmental model and to get PK parameters.After that
the pharmacokinetic parameters were fixed
and the time effect relationship were fitted to get the relevant PD parameters.According to the PD parameters
the PK-PD models of two representative components in Xinshao formula were established. Result:When SOD was used as the index of efficacy
the PK-PD models of scutellarin and paeoniflorin were obtained as E=21.08+5.49Ce/(Ce+7 368.24) and E=20.02+1.58Ce/(Ce+0.02). When LDH was used as the index of efficacy
the PK-PD models of scutellarin and paeoniflorin were obtained as E=211.98-89.13Ce/(Ce+2 013.2) and E=216.83-37.31Ce/(Ce+0.04). Conclusion:The concentrations of SOD and LDH are correlated with the concentrations of scutellarin and paeoniflorin.The formula and its main active components (scutellarin and paeoniflorin) can protect cerebral ischemia reperfusion injury by increasing concentration of SOD and decreasing concentration of LDH.