盐酸多奈哌齐胶囊及片剂的人体生物等效性研究

Bioequivalence of donepezil capsule and tablet in human

目的 建立人血浆中盐酸多奈哌齐的HPLC MS (quadrupole)测定方法 ,研究盐酸多奈哌齐在正常人体内的药代动力学行为 ,评价其两种制剂的生物等效性。方法 人体实验采用双交叉设计 ,2 0名健康受试者交叉口服国产盐酸多奈哌齐胶囊和进口片剂 ,服药后 0 5～ 1 92h内间隔取血。血样加入内标 (盐酸非洛普 )经预处理后用HPLC MS(quadrupole)法测定 ,检测离子为m z 380 (多奈哌齐 )、m z 344(内标 ) ,裂解电压为 1 2 0V。计算主要药动学参数 ,并以片剂为参比制剂 ,估算国产胶囊的相对生物利用度 ,判断生物等效性。结果 国产及进口盐酸多奈哌齐制剂的生物半衰期分别为 (63± 1 0 )h和 (57± 9)h ,达峰时间分别为 (3 3± 0 4)h和 (3 4± 1 0 )h ,峰浓度分别为 (8 5± 0 4)μg·L-1 和 (8 1± 1 0 ) μg·L-1 。以进口制剂为对照 ,用AUC0 1 92 计算的国产胶囊相对生物利用度为 1 0 2 %± 1 1 %。结论 本实验建立的分析方法灵敏、准确、简便 。

Aim To develop an HPLC MS assay for determination of donepezil in human plasma and to investigate the pharmacokinetics and bioequivalence of donepezil capsule in healthy volunteers. Methods A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 5 mg dose of either capsule or tablet was administered to each volunteer. After spiked with the internal standard (phenoprolamine) and treated with saturated sodium bicarbonate, plasma was extracted with ethyl acet...