盐酸多奈哌齐口腔崩解片人体药物代谢动力学和生物等效性试验

Pharmacokinetic and Bioavailability of Donepezil Orally Disintegrating Tablet in Healthy Volunteers

目的采用高效液相色谱-质谱联用法研究盐酸多奈哌齐口腔崩解片的人体药物代谢动力学,并评价其生物等效性。方法 2009年9月-11月对22例健康男性受试志愿者单次交叉口服盐酸多奈哌齐口腔崩解片(试验制剂)和盐酸多奈哌齐普通片(参比制剂),测定给药后不同时间点血浆中多奈哌齐经时血药浓度,采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。结果受试者单次口服试验制剂与参比制剂后,达峰时间分别为(2.95±1.16)、(3.19±0.98)h,峰浓度分别为(9.98±2.93)、(9.13±2.05)ng/mL,药时曲线下面积(0-t)分别为(470.76±142.64)、(446.57±137.30)ng/mL.h;药时曲线下面积(0-∞)分别为(517.74±169.79)、(489.47±162.13)ng/mL.h。试验制剂与参比制剂的生物等效性结果为104.7%,其90%置信区间为(98.4%,111.4%)。结论盐酸多奈哌齐口腔崩解片与普通片生物等效。

Objective To study the pharmacokinetic and bioavailability of donepezil orally disintegrating tablet in healthy volunteers with high performance liquid chromatography-mass spectrometry （HPLC-MS）. Methods Twenty- two healthy male volunteers were enrolled in the study between September and November 2009. The subjects orally took a single dose of 5 mg donepezil test or reference preparation. The concentrations of donepezil plasma were assessed and data were analyzed automatically with DAS 2.0 pharmacokinetic program. The relative bioavailability of donepezil test or reference preparation was calculated. Results The parameters of donepezil test and reference preparation were as following： the peak time （Tmax） was （2.95 ± 1.16） h and （3.19 ±0.98） h; the peak concentration （Cmax） was （9.98 ± 2.93） ng/mL and （9.13± 2.05） ng/mL; the area under the curve （AUC）（0_t） was （470.76 ±142.64） ng/mL · h and （446.57 ± 137.30） ng/mL· h; AUC（0-∞ was （517.74± 169.79） ng/mL· h and （489.47±162.13） ng/mL · h, respectively. The relative bioavailability of ubenimex capusules was 104.7%, 90%CI （98.4%, 111.4%）. Conclusion Donepezil orally disintegrating tablet shows a bioequivalence compared with reference preparation.