摘要
Objective: Monitoring the unbound drug concentration in blood in combination therapy is necessary,because its concentration determines the efficacy of drug therapy. This study was designed to explore the effect of Dan Hong Injection(DHI) on the unbound warfarin using two approaches including an in vivo pharmacokinetic and in vitro fluorescence studies.Methods: The effect of DHI on the pharmacokinetic properties of the unbound warfarin was investigated by a microdialysis sampling method coupled with LC–MS/MS. The effect of DHI and salvianolic acid B(Sa B) on warfarin binding with bovine serum albumin(BSA) was conducted by fluorescence spectrometry.Results: The AUC_(0-tn)of warfarin with DHI group was higher than that of warfarin alone group. The result showed that DHI could increase the concentration of unbound warfarin in rat blood, which may be due to the competition between warfarin and DHI as well as its components binding to serum albumin. The competition process was demonstrated by fluorescence study.Conclusion: Combination therapy of DHI with warfarin could enhance the release profile of warfarin from serum protein.
Objective: Monitoring the unbound drug concentration in blood in combination therapy is necessary,because its concentration determines the efficacy of drug therapy. This study was designed to explore the effect of Dan Hong Injection(DHI) on the unbound warfarin using two approaches including an in vivo pharmacokinetic and in vitro fluorescence studies.Methods: The effect of DHI on the pharmacokinetic properties of the unbound warfarin was investigated by a microdialysis sampling method coupled with LC–MS/MS. The effect of DHI and salvianolic acid B(Sa B) on warfarin binding with bovine serum albumin(BSA) was conducted by fluorescence spectrometry.Results: The AUC_(0-tn)of warfarin with DHI group was higher than that of warfarin alone group. The result showed that DHI could increase the concentration of unbound warfarin in rat blood, which may be due to the competition between warfarin and DHI as well as its components binding to serum albumin. The competition process was demonstrated by fluorescence study.Conclusion: Combination therapy of DHI with warfarin could enhance the release profile of warfarin from serum protein.
基金
supported by Program for Changjiang Scholars and Innovative Research Team in University(No.IRT_14R41)
Tianjin Research Program of Application Foundation and Advanced Technology(15JCYBJC29300)
