Determination fudosteine in plasma and its pharmacokinetics by LC-MS

OBJECTIVE To investigate the pharmacokinetics of single dose and multiple dose of fudosteine tablets in chinese healthy volunteers.METHODS 12 volunteers were divided into three groups and fudosteine concentrations in plasma of 12 volunteers after taking 200,400 and 600 mg fudosteine and taking multiple 400 mg fudosteine were determined by LC-MS.The pharmacokinetic parameters were calculated by DAS 2.0 software.RESULTS The main pharmacokinetics parameters of single dose:Cmax were 8.8±4.2,19.4±4.0 and 33.6±11.5 mg·L-1,respectively;AUC0-t were 15.6±3.7,30.4±6.5and 55.3±9.0 mg·h·L-1,respectively;tmax were 0.44±0.15,0.54±0.34 and 0.46±0.12 h,respectively;t1/2 were 3.1±0.6,3.0±0.5 and 2.65±0.33 h,respectively,CL/F were 12.7±3.2,12.5±2.4 and 10.7±1.7 h-1,respectively.The main pharmacokinetics parameters Cmax,AUC0-t,AUC0-∞ showed direct proportion to doses.There were no singnificant difference in tmax,Ke,t1/2,MRT and CL/F of three groups.The parameters of multiple dose:Cmax was 18.7±5.8 mg·L-1;AUC0-t and AUC0-∞ were 29.3±11.0 mg·h·L-1 and 31.1±11.9 mg·h·L-1,respectively;t1/2 was 3.1±0.5 h;Css was 2.4±0.9 mg·L-1;and DF% was(7.8±2.2)%.CONCLUSION The pharmacokinetics of fudosteine between 200 mg and 600 mg in human body was linear.There was no drug accumulation after taking multiple dose.