国产辛伐他汀片药代动力学及生物利用度研究

PHARMACOKINETICS AND RELATIVE BIOAVAILABILITY OF DOMESTIC SIMVASTATIN TABLET IN HEALTHY VOLUNTEERS

１２ 名健康志愿者交叉口服单剂量国产辛伐他汀片和舒降之片剂 ４０ ｍ ｇ，应用 Ｈ Ｐ Ｌ Ｃ 法测定其经时血药浓度。实验数据经 ３ Ｐ９７ 程序处理，两制剂口服吸收呈二室模型。辛伐他汀片和舒降之各相关药代动力学参数： Ｃｍ ａｘ 为（１０５．９７±２５．９８） μｇ／ Ｌ 和（１１０．３２±２７．６７） μｇ／ Ｌ， Ｔｍ ａｘ 为（１．９０±０３７） ｈ和（１．９９±０．３５） ｈ， Ａ Ｕ Ｃ 为（９７０．０６±１１７．７４）（μｇ／ Ｌ·ｈ ）和（９７６．８１±１５０．１３）（μｇ／ Ｌ·ｈ ），根据辛伐他汀片和舒降之的代谢产物辛伐他汀酸（ Ｓ Ｖ Ａ）血药浓度时间曲线下面积 Ａ Ｕ Ｃ，计算辛伐他汀片相对生物利用度为（９８．６２±１２．０１）％ 。经方差分析及双单侧 Ｔ 检验和（１－ ２α）置信区间分析，显示两制剂 Ａ Ｕ Ｃ值在制剂间、周期间和个体间均无显著性差异，提示辛伐他汀片和舒降之片具有生物等效性。

A single oral dose of domestic simvastatin tablet or imported simvastatin tablet 40 mg was given to 12 healthy male volunteers in a randomized cross over clinical study. The serum concentrations of simvastatin acid were determined by HPLC.The pharmacokinetics parameters were analyzed by 3P97 software. It was found that the serum concentration time curve fitted to two compartment model, and the main pharmacokinetics parameters of domestic and imported tablets were as follows Cmax= (105.97±25.98) μg/L and (110.32±27.67)μg/L, Tmax=(1.90±0.37) h and (1.99±0.35) h, AUC=(970.06±117.74) μg/(L·h) and (976.81±150.13) μg/(L·h). The relative bioavailability of domestic was (98.62±12.01)%. These results suggested that there were no significant difference between the domestic and imported tablets. They are bioequivalent.