健康男性志愿者体内阿那曲唑生物利用度和药代动力学研究

Bioavailability and pharmacokinetics of anastrozole in healthy male volunteers

目的 比较国产和进口阿那曲唑片在健康人体内的生物利用度和药代动力学。方法 二十名中国健康男性志愿者随机交叉单剂量口服 2mg国产和进口阿那曲唑片 ,用GC ECD法测定血药浓度。血药浓度测定的线性范围为1 32 5～ 10 6 μg·L-1。低、中、高血药浓度 (5 3、2 1 2、5 3 0 μg·L-1)提取回收率分别为 76 8%、87 0 %、78 7%。天内和天间精密度均小于 9%。通过方差分析和双单侧t检验比较两种制剂的药—时曲线下面积 (AUC0 -t)、最大血药浓度(Cmax)和达峰时 (Tmax)。结果 阿那曲唑的体内分布符合二室模型。国产和进口阿那曲唑的药动学参数Cmax分别为(36 5± 6 9)和 (35 6± 9 4 ) μg·L-1;Tmax分别为 (1 5 6±0 4 1)和 (1 5 3± 0 4 9)h ;AUC0 -t分别为 (14 0 3 6± 32 1 2 )和 (1371 6± 32 9 4 ) μg·h·L-1,T1/ 2 β分别为 (42 5 7± 10 15 )和 (43 4 1± 8 5 9)h。经t检验做等效性判断 ,说明两制剂具有生物等效性。结论 两种制剂为生物等效 ,国产阿那曲唑片的相对生物利用度为 (10 2 7± 5 6 ) %。

AIM To evaluate bioavailability and pharmacokinetics of domestic and imported anastrozole tablets. METHODS Twenty Chinese healthy male volunteers were enrolled in a randomized crossover study with a single oral dose of 2 mg of the two formulations respectively. The anastrozole in plasma was measured by gas chromatography with electron capture detection. The linear range was from 1 325 to 106 μg·L -1 plasma. The extraction recovery rates for plasma concentration of 5 3, 21 2 and 53 0 μg·L -1 were 76 8%, 87 0% and 78 7% respectively. Inter day and intra day precisions of the method were < 9%. Area under concentration time curve ( AUC 0-t ), maximum plasma concentration ( C max ) and reach peak time ( T max ) were evaluated by variance analysis and two one side t test. RESULTS A two compartment model was adopted in anasreozole plasma concentration time data analysis. The main pharmacokinetic parameters of domestic and imported anastrozole tablets such as C max , T max , AUC 0-t and T 1/2β were (36.5±6.9) and (35.6±9.4) μg·L -1 , (1.56±0.41) and (1 53±0 49) h, (1403 6±321 2) and (1371 6±329 4) μg·h·L -1 , (42 57±10 15) and (43 41±8 59) h, respectively, and there were no significant differences between the two formulations. CONCLUSION Domestic and imported anastrozole tablets are of bioequivalence. The relative bioavailability of the domestic tablet is (102 7±5 6)%.