临床常用普伐他汀钠片大鼠体内药代动力学比较研究

A comparative pharmacokinetics study of pravastatin sodium tablets in rats

目的:研究大鼠灌胃不同企业普伐他汀钠片后体内药代动力学的一致性。方法:固体灌胃给予SD雄性大鼠普伐他汀钠15 mg/kg,采用液质联用法测定不同时间的血药浓度,绘制药时曲线,并用DAS 3.0.7数据处理系统进行主要药代动力学参数的计算和比较。结果:三个原料药生产企业的测定结果显示,3号晶F型普伐他汀钠原料药较1、2号晶A型有着更好的药物吸收和相对生物利用度,为优势药物晶型;随机抽取的临床常用7种普伐他汀钠片在大鼠体内药代动力学参数结果呈现显著性差异,Tmax,Cmax,AUC,t1/2的最大差异分别可以达到5.3,3.4,2.4和1.4倍之多。结论:不同企业的普伐他汀钠片在大鼠体内的药代动力学过程存在显著性差异,这可能与普伐他汀钠多晶型状态以及药物生产工艺、辅料成分及含量等制剂过程有关。

AIM： To study the pharmacokinetics of different pravastatin sodium tablets in rats. METHODS： An LC-MS method was established for the detection of pravastatin sodium in plasma after a single oral dose of 15 mg/kg pravastatin sodium tablets and a time-plasma concentration curve was presented. Main pharmacokinetic parameters were calculated by DAS 3.0.7 Data Processing System. RESULTS：Determination results of the three bulk drug manufactures indicated that pravastatin form F had a higher absorption and relative bioavailability than form A. Pharmacokinetic parameters of the seven products selected randomly from different industries were different after a single dose of 15 mg/kg pravastatin sodium. Maximum differences of Cmax, Tmax, AUC and t1/2 came up to 3.4, 5.3, 2.4 and 1.4 times. CONCLUSION： Polymorphism has an important influence on the differences among the pharmacokinetics of different pravastatin sodium tablets in rats. In addition, production process, excipient and content of pravastatin sodium should be also considered in the quality control of pravastatin sodium tablets.