Abstract: AIM: To investigate the pharmacokinetics of Tolvaptan tablets at single doses and multiple doses in healthy Chinese volunteers. METHODS: A single oral doses of tolvaptan tablets (15,30,60 mg) were given to 12 healthy volunteers (half male and half female) according to an open, random 3×3 latin design. Another 12 healthy volunteers (half male and half female) received multiple doses. The concentrations of tolvaptan in plasma were determined by liquid chromatography/tandem mass spectrometry (LC-MS/MS) and the pharmacokinetic parameters were calculated using NCA method of WinNonlin program. RESULTS: The main pharmacokinetic parameters of tolvaptan after single doses (15,30,60 mg) were as follows: C_max were (129±36.6), (250±105), and (418±166) μg/L,t_max were (2.30±0.48), (2.30±0.89), and (2.45±0.60) h,AUC_last were (758±217), (1570±494), and (3360±1420) μg·h·L^-1,AUC_inf were (768±215), (1590 ± 490), and (3400±1410) μg·h·L^-1,t_1/2 were (7.08±3.78), (6.77±1.60), and (7.02±1.89) h. The parameters of tolvaptan after multiple doses(30 mg) were as follows: C_max was (254±90) μg/L,t_max was (2.63±1.25) h,AUC_last was (1760±709) μg·h·L^-1,AUC_inf was (1790±711) μg·h·L^-1,t_1/2 was (6.92±2.58) h. CONCLUSION: Over the single dose range of 15-60 mg, the exposure measured as AUC and C_max were found to be proportional with dosage. After 30 mg multiple doses administration, tolvaptan showed no accumulation at steady status.

Key words: tolvaptan, HPLC-MS/MS, pharmacokinetics