氢溴酸加兰他敏口服液及片剂的人体生物等效性研究

A bioequivalent study of galanthamine hydrobromide solution to immediate release tablet

目的:采用HPLC-RF检测法测定氢溴酸加兰他敏的血药浓度,研究其在人体内的药动学和生物等效性。方法:24例健康男性志愿者单剂量随机交叉口服5 mg加兰他敏口服液(受试制剂)和片剂(参比制剂)。血浆样品经碱化后用乙醚提取,采用反相HPLC-RF法测定血浆中加兰他敏浓度,检测波长:激发波长290 nm,发射波长320 nm。采用3P97药动学软件计算药动学参数和相对生物利用度,并对参数进行方差分析和双单侧t检验。结果:加兰他敏口服液和片剂的主要药动学参数:Cmax分别为(31．53±5．59)和(33．44±5．72)μg·L-1;Tmax分别为(1．66±0．79)和(1．51±0．72)h;t1/2分别为(7．06±2．16)和(6．64±2．30)h;AUC0～∞分别为(340．6±77．2)和(325．5±77．7)μg·h·L-1。氢溴酸加兰他敏口服液相对生物利用度为105．6％。结论:加兰他敏口服液和片剂生物等效。

Objective：To investigate the pharmacokinetics profiles and bioequivalence of galanthamine. Methods： Twenty-four healthy male volunteers were orally administered with a randomized and single crossover dose of galanthamine hydrobromide solutions （test sample） and immediate release tablets （reference sample） 5 mg. Following after the extraction of the alkalinized plasma samples of the volunteers using ether, the plasma galanthamine were quantified by reverse phase HPLC with a fluorescence-detection at Ex290 nm and Em320 nm. The pharmacokinetic parameters including variance and two-one side t test analysis and relative bioavailability were calculated using 3P97 pharmacokinetics software. Results： The main pharmacokinetic parameters of galanthamine hydrobromide solutions and tablets were as follows ：Cmax（31.53±5.59）vs. （33.44 ±5.72）μg·L^-1; Tmax（1.66 ±0.79）vs. （1.51 ±0.72）h; t1/2 （7.06 ±2.16）vs. （6.64 ±2.30）h; AUC0～∞（340.6±77.2）vs. （325.5±77.7）μg·L^-1. The relative bioavailability of galanthamine solutions was 105.6%. Conclusion： The two formulations were bioequivalent.