关键词: 琥珀酸索利那新, LC-MS/MS, 生物等效性, 药代动力学

Abstract: AIM: To evaluate the bioequivalence of the test and reference preparations of solifenacin succinate tablets administered once orally under fasting and fed conditions in Chinese healthy volunteers.  METHODS: The study was designed as single-center, randomized, open, self-crossover and twenty four healthy volunteers were recruited respectively in fasting and fed conditions. Subjects were assigned to receive a single oral of the test or reference formulation per period at a dose of 10 mg. The plasma concentration of solifenacin was analyzed by LC-MS/MS. The major pharmacokinetic parameters were calculated by WinNonlin 7.0, then the bioequivalence was evaluated.RESULTS: The main pharmacokinetic parameters of a single oral solifenacin succinate under fasting condition for test and reference preparation were as follows: Cmax (13.99±3.34) and (13.27±3.20) ng/mL, AUC0-t (675.60±210.46) and (653.31±238.59) h·ng·mL-1, AUC0-∞(728.28±240.20) and (718.14±275.63) h·ng·mL-1, tmax (5.00±1.41) h and (4.98±1.07) h, t1/2 (39.19±9.29) and (42.44±12.66) h. The relative bioavailability was 105.06% for AUC0-t, 104.07% for AUC0-∞. The main pharmacokinetic parameters of a single oral solifenacin succinate under fed condition for test and reference preparation were as follows: Cmax (15.65±5.30), (15.02±4.42) ng/mL; AUC0-t (808.85±271.19), (793.76±256.78) h·ng·mL-1; AUC0-∞ (917.02±347.82), (875.49±310.77) h·ng·mL-1. tmax (4.29±1.48) h and (5.69±4.10) h, t1/2 (49.47±20.08) and (45.29±12.24) h. The relative bioavailability was 100.91% for AUC0-t, 102.97% for AUC0-∞. The 90% confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞ of the two preparations under fasting/feding conditions were all within 80%-125%.CONCLUSION: The test and reference preparation of solifenacin succinate tablets are bioequivalent under fasting and fed conditions.

Key words: solifenacin succinate, LC-MS/MS, bioequivalence, pharmacokinetic