连续口服多剂量国产瑞舒伐他汀钙片的药动学

 目的通过对中国健康志愿者连续口服国产瑞舒伐他汀钙片后的药动学研究,探讨国产瑞舒伐他汀钙片在人体内的药动学特征。方法36名健康志愿者分为3组,按平行设计方法分别多剂量口服国产瑞舒伐他汀钙片5,10和20 mg,每天1次,连续给药8 d,采用LC-MS测定不同时间血中瑞舒伐他汀的浓度,在计算机上以DAS2.0软件进行数据处理,求算药动学参数。结果3个不同剂量组瑞舒伐他汀的主要药动学参数t_1/2分别为(21.65±7.63),(20.90±7.93),(16.77±3.80)h,t_max分别为(4.0±2.3),(3.7±1.4),(3.5±1.4)h,ρ_max分别为(6.49±1.74),(12.72±5.60),(22.17±9.09)μg·L^-1,ρ_SS分别为(1.24±0.28),(2.57±0.86),(4.21±1.16)μg·L^-1,AUC_0-72分别为(89.51±20.45),(185.34±61.75),(303.41±83.81)μg·h·L^-1,波动百分率DF%分别为(4.28±0.88)%,(4.00±1.30)%,(4.23±1.17)%。结论本品多剂量口服给药在5～20 mg时,瑞舒伐他汀钙片具有高度的正相关性,连续给药8 d不会在国人体内产生蓄积作用。

Pharmacokinetics of Multiple Oral Doses of Rosuvastatin Calcium Tablets

OBJECTIVE To investigate the pharmacokinetic parameters of multiple doses of rosuvastatin calcium tablets in Chinese healthy volunteers,and compare their pharmacokinetic characteristics in volunteers.METHODS 36 Healthy volunteers were divided into three groups by parallel design.The drug concentrations of plasma sample after taking 5,10 and 20 mg rosuvastatin once daily for eight days were determined by LC-MS.The pharmacokinetic parameters were calculated by DAS 2.0 software.RESULTS The healthy volunteers took rosuvastatin calcium tablets with thedose of 5,10 and 20 mg for eight days,respectively.The main pharmacokinetic parameters were as follows:t_1/2 were(21.65±7.63),(20.90±7.93) and(16.77±3.80)h,respectively;t_max were(4.0±2.3),(3.7±1.4) and(3.5±1.4)h,respectively;ρ_max were(6.49±1.74),(12.72±5.60) and(22.17±9.09)μg·L^-1,respectively;AUC_0-72 were(89.51±20.45),(185.34±61.75) and (303.41±83.81) μg·h·L^-1,respectively;DF% were(4.28±0.88)%,(4.00±1.30)% and(4.23±1.17)%,respectively.CONCLUSION The serum concentrations after multiple oral doses of rosuvastatin calcium tablets level were correlated with the drug dose administrated.There was no drug accumulation up to eight dosing in Chinese healthy volunteers.