The Pharmacokinetic Changes Of Rivaroxaban And Repaglinide After Co-adminisitration In Rats

Part 1 Simultaneous determination of rivaroxaban and repaglinide in ratplasma by HPLC-MS/MSObjective: To establish a method for simultaneous determination of rivaroxaban and repaglinide in rat plasma by HPLC-MS/MS.Methods: Rivaroxaban and repaglinide in rats plasma were separated by Diamonsil C18 with the mobile phase consisting of acetonitrile-0.1% formic acid?60:40?.Gliclazidewas used as the internal standard.Detection and quantification were performed by using ESI-MS.The detector was operated in selected reaction-monitoring mode at m/z 436.0?m/z 144.9 for rivaroxaban,m/z 452.9 ?m/z 162.3 for repaglinide and m/z 324.1?m/z 127.2for gliclazide.Results: The calibration curve obtained were linear over the concentration range of 12.5⁸00 ng·mL^-1?r=0.9971?for rivaroxaban and2.5¹60 ng·mL^-1?r=0.9995?for repaglinide.Conclusions: The method is found to be simple,sensitive and accurate for determining the concentration of rivaroxaban and repaglinide in rat plasma.Part 2 The pharmacokinetic changes of rivaroxaban and repaglinide afterco-adminisitration in ratsObjective: To study the pharmacokinetic changes of rivaroxaban and repaglinide after co-adminisitration in rats.Methods: Fifty-four male wistar rats were divided into three groups:repaglinide group,rivaroxaban group and co-administration group.Blood samples were collected at different times before and after oral administration.Results: The pharmacokinetic parameters of rivaroxaban in the test group and control group were as follows: AUC_0-24 were?2646.19±958.97?ng·h·mL^-1 and?1976.05±835.92?ng·h·mL^-1;AUC_0-? were?3068.44±1115.64?ng·h·mL^-1 and?2232.03±978.17?ng·h·mL^-1;t_1/2 were?8.33±4.45?h and?6.87±2.68?h;T_max were?0.96±0.39?h and?0.88±0.45?h;CL were?0.97±0.39?L·?h·kg?^-1 and?1.39±0.58?L·?h·kg?^-1;V were?10.66±5.29?L and?13.02±6.23?L;C_max were?507.22±169.13?ng·mL^-1 and?382.61±89.38?ng·mL^-1.The pharmacokinetic parameters of repaglinide in the test group and control group were as follows: AUC0^-12 were?180.49±56.52?ng·h·mL^-1 and?151.33±44.32?ng·h·mL^-1;AUC_0-? were?212.79±66.02?ng·h·mL^-1 and?192.45±85.96?ng·h·mL^-1;t_1/2 were?5.18±2.28?h and?4.90±2.67?h;T_max were?0.55±0.26?h and?0.48±0.15?h;CL were?2.09±0.75?L·?h·kg?^-1 and?2.37±0.74?L·?h·kg?^-1;V were?14.60±5.30?L and?16.16±10.01?L;C_max were?89.22±30.26?ng·mL^-1 and?77.27±27.41?ng·mL^-1.Conclusions: Rivaroxaban and repaglinide exist pharmacokinetic changes after co-adminisitration in rats.