多奈哌齐胶囊与片剂在人体中的生物等效性

[Bioequivalence of donepezil capsule and tablet in human].

作者信息

Hao Xin-yu, Ding Li, Li Li-ming, Bian Xiao-jie, Zhang Sheng-qiang

机构信息

Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Yao Xue Xue Bao. 2003 May;38(5):392-4.

PMID:12958848

Abstract

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 acetate and separated with a C18 reversed phase column. LC-ESIMS was used in the selected ion monitoring (SIM) mode with target ions at m/z 380 for donepezil and m/z 344 for phenoprolamine. The fragmentor voltage was 120 V. The main pharmacokinetic parameters of donepezil and the bioequivalence of its two preparations were calculated.

RESULTS

The main pharmacokinetic parameters T1/2, Tmax and Cmax were (63 +/- 10) h, (3.3 +/- 0.4) h and (8.5 +/- 0.4) microgram.L-1 for the capsule; (57 +/- 9) h, (3.4 +/- 1.0) h and (8.1 +/- 1.0) microgram.L-1 for the tablet, respectively. The relative bioavailability of the donepezil capsule was 102% +/- 11%.

CONCLUSION

The assay was shown to be sensitive, accurate and convenient. The two preparations of donepezil were bioequivalent.

摘要

目的

建立高效液相色谱 - 质谱法测定人血浆中多奈哌齐，并研究多奈哌齐胶囊在健康志愿者体内的药代动力学和生物等效性。

方法

20名健康志愿者采用随机交叉设计。在两个研究阶段，给每位志愿者单次服用5mg胶囊或片剂。加入内标（去氧肾上腺素）并用饱和碳酸氢钠处理后，血浆用乙酸乙酯萃取，并用C18反相柱分离。液相色谱 - 电喷雾离子源质谱在选择离子监测（SIM）模式下进行，多奈哌齐的目标离子为m/z 380，去氧肾上腺素的目标离子为m/z 344。碎裂电压为120V。计算多奈哌齐的主要药代动力学参数及其两种制剂的生物等效性。