比卡鲁胺片的相对生物利用度及生物等效性评价

采用同体交叉试验方法,对天津新新制药厂提供的比卡鲁胺片(受试制剂)与德国AstraZeneca公司进口的比卡鲁胺片(参比制剂)在健康人体内的生物等效性进行评价。18名健康志愿者分别单剂量口服受试制剂和参比制剂,应用高效液相色谱法测定血浆中比卡鲁胺药物浓度,绘制药时曲线,计算受试制剂和参比制剂的主要药代动力学参数,2种制剂的达峰时间Tmax分别为(4.94±0.24)h和(3.11±0.32)h,达峰时血中药物浓度Cmax分别为(3885.19±1924.55)ng/mL和(4319.88±2250.15)ng/mL,2种制剂的消除相半衰期t1/2分别为(12.59±3.31)h和(13.45±3.90)h,药时曲线下面积AUC0→48分别为(37966.35±9228.13)ng.h.mL-1和(36552.52±9591.71)ng.h.mL-1,AUC0→∞分别为(41451.43±10326.81)ng.h.mL-1和(40286.27±11573.62)ng.h.mL-1,相对生物利用度F为(104.85±9.62)%。研究结果表明受试制剂的AUC0→48、AUC0→∞的90%可信限落在参比制剂80%—125%范围内,Cmax落在70%—143%范围内。虽然受试制剂较参比制剂达峰慢,但2种制剂的Cmax、AUC0→48和AUC0→∞一致,可以认为受试制剂与参比制剂2种制剂生物等效。

Relative Bioavailability and Bioequivalence Evaluation of Bicalutamide Tablets

Pharmacokinetics characteristic and relative bioavailability of the bicalutamide test and reference tablets in healthy body was studied.With the crossover testing methods,a single oral dose of the bicalutamide test and reference tablets were given to 18 healthy volunteers.The concentrations of bicalutamide in plasma were determined by high performance liquid chromatography（HPLC）,and the concentration-time curves were drawn.The major pharmacokinetic parameters and relative bioavailability of the test and reference tablets were calculated by a pharmacokinetical program,at the same time the bioequivalence of two formulations were evaluated.The result are as follows：Tmax=（4.94±0.24）h and （3.11±0.32）h,Cmax=（3885.19±1924.55）ng/mL and（4319.88±2250.15）ng/mL,t1/2=（12.59±3.31）h and （13.45±3.90）h,AUC0→48=（37966.35±9228.13）ng·h·mL-1 and（36552.52±9591.71）ng·h·mL-1,AUC0→∞=（41451.43±10326.81）ng·h·mL-1 and（40286.27±11573.62）ng·h·mL-1,respectively.The analysis showed that the 90% confidence intervals of AUC0→48 and AUC0→∞ of bicalutamide test both fell within the range from 80% to 125% of bicalutamide reference.The relative bioavailability of bicalutamide tablets was （104.85±9.62）%.Although the test tablets reached the peak more slowly than the reference tablets,no significant differences were found between T and R.Therefore,it could be considered that bicalutamide test and reference tablets are bioequivalent.