阿魏酸钠胶囊人体生物利用度与生物等效性研究

The Study of Bioavailability and Bioequivalence of Sodium Ferulate Capsule in Humans

目的建立测定人血浆阿魏酸浓度的高效液相色谱紫外（HPLCUV）法,以阿魏酸钠片为参比制剂,研究阿魏酸钠胶囊人体相对生物利用度,评价受试制剂与参比制剂生物等效性。方法采用随机交叉试验设计。分别给予男性健康志愿者20例受试制剂或参比制剂100 mg,采用HPLCUV法检测血浆阿魏酸浓度。DAS ver 2.0软件估算药动学参数, 判定两制剂生物等效性。结果血浆阿魏酸线性范围为0.019 6～7.851 0 μg·mL^-1 ,平均回收率＞ 90% , 日内和日间RSD 均＜10%。阿魏酸钠受试制剂与参比制剂主要药动学参数药时曲线下面积（AUC0→t）分别为（0.813±0.397）和（0.841±0.329）μg·h·mL^-1,AUC0→∞分别为（0.843±0.405）和（0.869±0.328） μg·h·mL^-1,Cmax分别为（1.517±0.660）和（1.579±0.698） μg·mL^-1,tmax分别为（0.404±0.130）和（0.392±0.118） h,t1/2分别为（0.701±0.374） 和（0.558±0.292）h。以AUC0→t计算,阿魏酸钠受试制剂与参比制剂比较,相对生物利用度（97.0±24.9）%。结论该试验所建立的人血浆阿魏酸浓度检测方法简便、准确,灵敏度较高,可用于阿魏酸钠人体药动学研究。两种制剂阿魏酸钠药动学参数差异无显著性,具有生物等效性。

ObjectiveA HPLC-UV method was developed and validated to determine ferulic acid in human plasma, and the pharmacokinetics of sodium ferulate capsule （test preparation） and tablet （reference preparation） in healthy volunteers were studied in order to evaluate the bioavailability and bioequivalence. MethodsA randomized cross-over bioavailability trial was designed in which 20 Chinese healthy male volunteers were divided into 2 groups and were orally given with sodium feulate capsules or tablets, respectively. The plasma concentration of ferulic acid was determined by HPLC-UV method. The pharmacokinetic parameters and relative bioavailability were calculated by DAS ver 2.0 to evaluate the bioequivalence of the test and reference preparations. ResultsThe calibration curve was linear over a concentration range of （0.019 6～7.851 0 ） μg·mL-1. The average recovery was more than 90.0%. The RSD of intra- and inter-day precision were less than 3.9% and 4.7%, respectively. The main pharmacokinetic parameters of capsule and tablet were as follows： AUC0→t were （0.813±0.397） and （0.841±0.329） μg·h·mL-1,AUC0→∞ were （0.843±0.405） and （0.869±0.328） μg·h·mL-1,Cmax were （1.517±0.660） and （1.579±0.698） μg·mL-1, tmax were （0.404±0.130） and （0.392±0.118） h,t1/2 were （0.701±0.374） and （0.558±0.292） h. According to AUC0→t, the relative bioavailability for test to reference preparation was （97.0±24.9）% . ConclusionThe method is sensitive and accurate and can be applied to the pharmacokinetic study of sodium ferulate after an oral administration to healthy Chinese volunteers. There are no statistically significant differences between the main pharmacokinetic parameters of two formulations. The test and reference preparations of sodium feulate are bioequivalent.