阿托伐他汀钙片在中国健康受试者的生物等效性试验

目的: 研究阿托伐他汀钙片与原研制剂立普妥的人体生物等效性。方法: 64例健康受试者参加空腹试验，64例健康受试者参加餐后试验，均采用两周期双交叉试验设计，先后口服受试制剂或参比制剂10 mg，采用液相色谱-串联质谱法测定人血浆中阿托伐他汀及其两种活性代谢物的浓度。使用WinNonlin 7.0软件进行数据处理。结果: 空腹给药后阿托伐他汀钙片受试制剂与参比制剂的C _max分别为（4.31±2.24）、（4.64±2.73） ng/mL，T _max分别为（0.58±0.36）、（0.58±0.35） h，t _1/2分别为（9.10±2.67）、（9.16±3.13） h，AUC _0-t分别为（23.79±10.73）、（21.93±9.29） ng·h·mL ^-1，AUC _0-∞分别为（24.87±10.88）、（23.04±9.29） ng·h·mL ^-1。餐后给药后阿托伐他汀钙片受试制剂与参比制剂的C _max分别为（2.41±1.37）、（2.39±1.21） ng/mL，T _max分别为（2.38±1.43）、（2.15±1.54） h，t _1/2分别为（10.86±8.77）、（9.59±2.81） h，AUC0-t分别为（19.03±9.26）、（19.25±9.20） ng·h·mL ^-1，AUC _0-∞分别为（20.25±9.30）、（20.39±9.27） ng·h·mL ^-1。结论: 阿托伐他汀钙片受试制剂与参比制剂在空腹和餐后条件下均生物等效。

Bioequivalence study of atorvastatin calcium tablets in Chinese healthy volunteers

AIM: To study human bioequivalence between atorvastatin tablets and original preparation Lipitor. METHODS: Sixty-four healthy subjects participated in the fasting test and 64 healthy subjects participated in the postprandial test. Both were designed using a randomized two-way crossover study. They were orally administered with 10 mg of the test preparation or reference preparation. The plasma concentration of atorvastatin and its two active metaboliteswere determined by LC-MS/MS. By means of WinNonlin 7.0 software, pharmacokinetic parameters were calculated.RESULTS:The pharmacokinetic parameters for atorvastatin of the two preparations under fasting condition were as follow: C _max of test and reference preparations were （4.31±2.24）, （4.64±2.73） ng/mL, T _max were （0.58±0.36）, （0.58±0.35） h，t _1/2 were （9.10±2.67）, （9.16±3.13） h，AUC _0-t were （23.79±10.73）,（21.93±9.29） ng·h·mL ^-1，AUC _0-∞ were （24.87±10.88）, （23.04±9.29） ng·h·mL ^-1. The pharmacokinetic parameters for atorvastatin of the two preparations under fed condition were as follow: C _max of test and reference preparations were（2.41±1.37）,（2.39±1.21） ng/mL，Tmax were （2.38±1.43）,（2.15±1.54） h，t _1/2 were （10.86±8.77）,（9.59±2.81） h，AUC0-t were （19.03±9.26）, （19.25±9.20） ng·h·mL ^-1，AUC _0-∞ were （20.25±9.30）, （20.39±9.27） ng·h·mL ^-1. CONCLUSION: The atorvastatin calcium test formulation and the reference formulation were both bioequivalent in both fasting and postprandial conditions.