Effect Of Scutellaria Barbata Extract On The Metabolism Of Icotinib In Beagles

OBJECTIVE:Toestablishanultra-highperformanceliquid chromatography-tandem mass spectrometry（HPLC-MS/MS）method for simultaneous detection of plasma icotinib and its metabolite M1 to study the effect of Scutellaria barbata extract on the metabolism of icotinib in beagle dogs.METHODS:Six beagle dogs were given 10mg·kg^-11 of icotinib.Then,blood samples were taken at different time points（0.33,0.67,1,1.5,2,3,4,6,8,12,24h）to detect the blood concentration of icotinib and its metabolite M1,followed by one week of drug elimination.Six beagle dogs were given5g·kg^-11 of Scutellaria barbata L.extract every morning for 6 consecutive days.On the 7th day,the extract of Scutellaria barbata L.was administered with 10mg·kg-1 of icotinib for 30 min.Venous blood was collected for different time periods（0.33,0.67,1,1.5,2,3,4,6,8,12,24 h）after administration to detect the blood concentration of icotinib and its metabolite M1.DAS 2.0 pharmacokinetics software calculates the main pharmacokinetics parameters.RESULTS:The t_1/2/2 of icotinib in the plasma of beagle dogs in the single-agent group and the combination group were（6.964±0.564）h and（8.923±1.172）h,and C_maxax were（508.858±49.19）ng·mL^-1.And（797.64±17.73）ng·mL^-1,AUC（0-∞）were（4279.79±359.23）ng·h·mL^-1and（6903.91±217.58）ng·h·mL^-1.The t_1/2/2 of M1 in the drug alone group and the combination group were（5.727±0.88）h and（4.243±1.52）h,and Cmax were（85.128±2.76）ng·mL^-1and（49.74±12.33）ng·mL^-1,AUC（0-∞）were（596.26±34.94）ng·h·mL^-11 and（365.68±51.41）ng·h·mL^-1.The results showed that after the combination of Scutellaria barbata L.extract.The C_maxax and AUC（0-∞）of icotinib increased significantly,and the C_maxax and AUC（0-∞）of metabolite M1 decreased,the difference was statistically significant.It indicated that the extract of Scutellaria barbata L.increased the plasma exposure of icotinib and decreased the blood concentration of M1.CONCLUSION:Scutellaria barbata extract inhibits the metabolism of icotinib in beagle dogs.It is recommended to adjust the dose appropriately when the two drugs are used in combination in the clinic.