匹伐他汀钙片在中国健康受试者体内的生物等效性研究

Bioequivalence study of pitavastatin calcium tablets in Chinese healthy subjects

目的评价2种匹伐他汀钙片在中国健康受试者中的生物等效性和安全性。方法采用单次给药、随机、开放、两周期、双交叉设计,空腹入组36例健康受试者,餐后入组48例健康受试者,随机交叉单次口服匹伐他汀钙受试制剂和参比制剂各2 mg,采用液相色谱-串联质谱法(LC-MS/MS)检测人血浆中匹伐他汀的浓度,用Phoenix WinNonlin8.1软件计算药代动力学参数,并进行两种制剂的生物等效性评价。结果受试者服用受试制剂和参比制剂后,空腹血浆中匹伐他汀主要药代动力学参数如下:Cmax分别为(41.90±16.53),(41.75±21.05)ng·mL-1,AUC0-t分别为(119.62±39.52),(115.29±44.80)ng·h·mL-1,AUC0-∞分别为(127.78±43.46),(122.95±48.59)ng·h·mL-1。餐后组血浆中匹伐他汀主要药代动力学参数如下:受试制剂和参比制剂的Cmax分别为(35.75±16.63),(39.78±23.93)ng·mL-1,AUC0-t分别为(120.16±46.74),(121.80±51.16)ng·h·mL-1,AUC0-∞分别为(126.24±49.91),(127.99±54.65)ng·h·mL-1。2种制剂的Cmax、AUC0-t和AUC0-∞经对数转换后90%置信区间分别为空腹状态下96.95%~109.37%,101.70%~109.43%,101.79%~109.64%;餐后状态下83.06%~101.84%,94.59%~103.45%和94.59%~103.58%。结论2种匹伐他汀钙片在中国健康受试者中具有生物等效性,安全性良好。

Objective To evaluate the bioequivalence of two kinds of pitavastatin calcium tablets in healthy Chinese subjects.Methods This was a single-dose,randomized,open-lable,two-period,two-way crossover pharmacokinetic study.A total of 36 healthy subjects for fasting study and 48 healthy subjects for fed study were enrolled,respectively,and randomized into two groups to receive a single dose of test or reference preparations 2 mg.Plasma concentration of pitavastatin was determined by LC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin software 8.1 software.Results The main pharmacokinetic parameters of pitavastatin of test and reference preparations were as follows:Under fasting state Cmax were(41.90±16.53),(41.75±21.05)ng·mL-1;AUC0-t were(119.62±39.52),(115.29±44.80)ng·h·mL-1,AUC0-∞were(127.78±43.46),(122.95±48.59)ng·h·mL-1.Under fed state Cmax were(35.75±16.63),(39.78±23.93)ng·mL-1,AUC0-t were(120.16±46.74),(121.80±51.16)ng·h·mL-1,AUC0-∞were(126.24±49.91),(127.99±54.65)ng·h·mL-1.The 90%CIs for Cmax,AUC0-tand AUC0-∞of test formulation in the fasting state were96.95%~109.37%,101.70%~109.43%,101.79%~109.64%;in the fed state were 83.06%~101.84%,94.59%~103.45%,94.59%~103.58%.Conclusion The test formulation and reference formulation of pitavastatin calcium tablets were equivalent and determined to be bioequivalent.