Determination of tegaserod in human plasma by LC-MS/MS and study on its pharmacokinetics

AIM To study the pharmacokinetics of tegaserod in human plasma by LC-MS/MS.METHODS Twenty-four healthy volunteers received tegaserod tablets (single doses,multidose),drug concentrations in plasma were determined.RESULTS Pharmacokinetic parameters of tegaserod after single oral doses (4,6,12 rag)were as follows: t(1/2)β(2.92+0.89),(3.81 +0.84)and (3.3+0.47)h;t_(max)(1.06+0.28),(1.00+0.26)and (1.00+0.18)h;ρ_(max)(1.23+0.47),(2.34 + 0.60)and (4.24 + 1.71)μg·L~(-1);AUC_(0→12)(3.04 + 0.91),(5.21±1.13)and (9.29 + 3.37)μg·h·L~(-1);MRT (3.57 + 0.81),(3.91 + 0.65)and (3.34±0.48)h,the essential pharmacokinetic pa- rameters after oral multidose (6 mg,bid)were as follows:t_(max)(0.96±0.10)h,ρss_(max)(2.60±0.53)μg·L~(-1),ρss_(min), (0.07 +0.01)μg·L~(-1),ρ_(av)(0.51 +0.11)μg·L~(-1),AUC_(0→12)(6.13±1.3)μg·h·L~(-1).CONCLUSION The method is accurate,sensitive.A two-compartment open pharmacokinetic model is adapted to tegaserod plasma concentration-time data analysis.The main phannacokinetic parameters are similar to those reported domestically and abroad.