盐酸多奈哌齐口腔崩解片人体生物等效性研究

Bioequivalence of Donepezil Hydrochloride Orally Disintegrating Tablets in Healthy Volunteers

目的:研究盐酸多奈哌齐口腔崩解片与盐酸多奈哌齐片人体的生物等效性。方法:20名男性健康志愿者随机交叉单剂量口服盐酸多奈哌齐口腔崩解片(受试制剂)与盐酸多奈哌齐片(参比制剂)5 mg,用液质联用法测定人血浆中多奈哌齐的浓度,用DAS 2.1软件计算药动学参数,并评价两制剂的生物等效性。结果:口服受试制剂和参比制剂药动学参数分别为C_(max)(8.56±2.10)和(8.08±1.78)ng·ml^(-1),t_(max)(2.65±0.74)和(3.05±0.83)h,t_(1/2)(70.31±19.54)和(71.15±18.47)h,AUC_(0～216)(373.76±94.15)和(353.04±81.42)ng·h·ml^(-1),AUC_(0-∞)(420.30±110.99)和(399.80±108.56)ng·h·ml^(-1)。受试制剂AUC_(0～216)的90%置信区间在参比制剂的等效范围内。结论:两种盐酸多奈哌齐制剂生物等效。

Objective：To study the bioequivalence of donepezil hydrochloride orally disintegrating tablets and donepezil hydrochloride tablets.Method：20 healthy male volunteers were enrolled in a randomized crossover study in which the subjects were randomly assigned to receive single dose of 5 mg orally disintegrating tablets（test preparation） or donepezil hydrochloride tablets（reference preparation ）. Plasma concentrations of donepezil were determined by liquid chromatography tandem mass spectrometry method.The pharmacokinetic parameters were calculated by DAS 2.1 software.Result：The main pharmacokinetic parameters of test and reference preparations after oral administration were as follows：C_（max）of（8.56±2.10） and（8.08±1.78） ng·ml^（-1）,t_（max） of（2.65±0.74） and（3.05±0.83） h,t_（1/2） of（70.31±19.54） and（71.15±18.47） h,AUC_（0-2l6） of（373.76±94.15） and（353.04±81.42） ng·h·ml^（-1）, AUC_（0-∞） of（420.30±110.99） and（399.80±108.56） ng·h·ml^（-1）.The 90%confidential intervals（CI） of AUC_（0-216） of the test preparation was in the bioequivalent range of the reference preparation.Conclusion：The two kinds of donepezil formulations are bioequivalent.