【摘要】 目的评价单次口服琥珀酸美托洛尔缓释片在中国健康受试者体内的药代动力学特征和安全性。方法 7例中国健康志愿者空腹单次口服琥珀酸美托洛尔缓释片47. 5 mg,8例中国健康志愿者在高脂餐后单次口服琥珀酸美托洛尔缓释片47. 5 mg,用液相色谱-串联质谱联用法测定给药后不同时间美托洛尔的血药浓度,并用Win Nonlin 6. 4软件计算主要药代动力学参数。结果本研究未观察到药物相关的不良事件和严重不良事件。空腹单次口服琥珀酸美托洛尔缓释片后的药代动力学参数如下:C_max为（14. 63±8. 93） ng·m L^-1,t_max为（9. 43±2. 76） h,t1/2为（9. 36±5. 76） h,AUC_0-t为（343. 63±262. 07） ng·m L^-1·h,AUC_inf为（359. 65±259. 29） ng·m L^-1·h,清除率为（188. 58±109. 10） L·h^-1,表观分布容积为（3031. 36±4029. 78） L。高脂餐后单次口服琥珀酸美托洛尔缓释片后的药代动力学参数如下:C_max为（19. 56±14. 89） ng·m L^-1,t_max（6. 00±1. 07） h,t1/2为（6. 27±1. 37） h,AUC_0-t为（391. 07±307. 06） ng·m L^-1·h,AUC_inf为（395. 84±311. 42） ng·m L^-1·h,清除率为（225. 97±201. 53） L·h^-1,表观分布容积为（2022. 20±1842. 51） L。结论高脂餐后给予琥珀酸美托洛尔缓释片,t_max较空腹给药提前,暴露量未见明显差异。更多还原

【Abstract】 Objective To evaluate the pharmacokinetics and safety of single dose of metoprolol succiniate sustained-released tablets under fasting and fed conditions in healthy Chinese volunteers. Methods Seven subjects were assigned to take a single dose of 47. 5 mg metoprolol succiniate sustained-released tablet in the fasting state. Eight subjects were administered a single dose of 47. 5 mg metoprolol succiniate sustained-released tablet after a high-fat meal. The plasma concentrations of metoprolol were assayed with liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated with Wn Nonlin ver. 6. 4. Results No drug-related adverse events and serious adverse events were observed. The pharmacokinetic parameters in the fasting state were as follows: C_max（ 14. 63 ± 8. 93） ng · m L^-1, t_max（ 9. 43 ± 2. 76） h,t1/2（ 9. 36 ± 5. 76） h,AUC_0-t（ 343. 63 ± 262. 07）ng·m L^-1·h,AUC_inf（ 359. 65 ± 259. 29） ng · m L^-1· h,clearance（ 188. 58 ± 109. 10） L·h^-1,apparent volume of distribution（ 3031. 36 ± 4029. 78） L. The pharmacokinetic parameters in the fed state were as follows: C_max（ 19. 56 ± 14. 89） ng·m L^-1,t_max（ 6. 00 ± 1. 07） h,t1/2（ 6. 27 ± 1. 37） h,AUC_0-t（ 391. 07 ± 307. 06） ng·m L^-1·h,AUC_inf（ 395. 84 ± 311. 42） ng·m L^-1·h,clearance（ 225. 97 ± 201. 53）L·h^-1,apparent volume of distribution（ 2022. 20 ± 1842. 51） L. Conclusion After a single oral dose of metoprolol succiniate administered to the healthy Chinese volunteers,t_maxin the fed state was shorter compared with that in the fasting state,no obvious difference of was observed between the exposures in the fasting and fed state.更多还原